Skip to main content

Advertisement

SpringerLink
Log in

Biologics in the Treatment of Transplant Rejection and Ischemia/Reperfusion Injury

New Applications for TNFα Inhibitors?

  • Mechanisms and Targets
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Tumor necrosis factor (TNF)-α inhibitors have proven efficacy in various autoimmune diseases such as Crohn disease, rheumatoid arthritis, psoriasis, and ankylosing spondylitis. Indeed, some TNFα inhibitors have already been approved for the management of the inflammatory manifestations associated with Crohn disease and rheumatoid arthritis. These agents are increasingly used for treatment of corticosteroid-resistant graft-versus-host disease after bone marrow transplantation, and case reports have documented their efficacy in treating corticosteroid- and muromonab-resistant rejection after intestinal transplantation. Thus, the potential role of TNFα inhibitors in transplantation of other vascularized solid organs is worthy of investigation.

Experimental evidence indicates that TNFα plays a key role in mediating ischemia/reperfusion (IR) injury after liver, kidney, intestine, heart, lung, and pancreas transplantation. TNFα was also identified as a marker cytokine during organ rejection. Single-center studies evaluating the role of TNFα inhibitors in kidney transplantation have been initiated but the results are not yet available.

TNFα is known to be a contributing factor in kidney allograft rejection, and may have value in predicting the onset of steroid-resistant acute rejection after liver transplantation. Experimental and preliminary clinical data have shown that circulating levels of TNFα are increased during cardiac graft rejection, and indicate that TNFα plays a role in the pathogenesis of acute cardiac allograft rejection. Anti-TNFα therapy was shown to prolong cardiac allograft survival when used alone or in combination with other drugs.

TNFα genotype has been strongly associated with mortality in humans due to acute cell-mediated heart transplant rejection. In addition, there is evidence for a genetic predisposition toward acute rejection after kidney and simultaneous kidney-pancreas transplantation. TNFα inhibition has been used successfully as part of an induction therapy for pancreatic islet cell transplantation. Apart from IR injury and acute rejection after lung transplantation, TNFα was also found to be involved in the pathoimmunology of obliterative bronchiolitis.

In conclusion, a substantial body of experimental evidence and preliminary clinical data suggest that TNFα inhibitors may play an important role in solid-organ transplantation, both in the amelioration of IR injury and in the treatment and prevention of acute rejection. Pharmacodynamic monitoring and pharmacogenetic screening may help to identify patients most likely to benefit from TNFα blockade. Randomized controlled trials in patients undergoing solid-organ transplantation are needed to further elucidate the clinical value of TNFα inhibition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I

Similar content being viewed by others

References

  1. Couriel DR, Hicks K, Giralt S, et al. Role of TNF-alpha inhibition with inflixiMAB in cancer therapy and hematopoietic stem cell transplantation. Curr Opin Oncol 2000; 12(6): 582–7

    PubMed  CAS  Google Scholar 

  2. Tracey KJ, Beutler B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Science 1986; 234: 470–4

    PubMed  CAS  Google Scholar 

  3. Beutler B, Krochin N, Milsark IW, et al. Control of cachectin (TNF) synthesis: mechanisms of endotoxin resistance. Science 1986; 232: 977–80

    PubMed  CAS  Google Scholar 

  4. Krakauer T, Stiles BG. Pentoxifylline inhibits superantigen-induced toxic shock and cytokine release. Clin Diagn Lab Immunol 1999; 6: 594–8

    PubMed  CAS  Google Scholar 

  5. Brennan FM, Chantry D, Turner M, et al. Detection of transforming growth factor-beta in rheumatoid arthritis synovial tissue: lack of effect on spontaneous cytokine production in joint cell cultures. Clin Exp Immunol 1990; 81: 278–85

    PubMed  CAS  Google Scholar 

  6. Levings MK, Schrader JW. IL-4 inhibits the production of TNF-alpha and IL-12 by STAT6-dependent and -independent mechanisms. J Immunol 1999; 162: 5224–9

    PubMed  CAS  Google Scholar 

  7. Scallon BJ, Moore MA, Trinh H, et al. Chimeric anti-TNF-alpha mAb cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 1995; 7: 251–9

    PubMed  CAS  Google Scholar 

  8. Kovarik JM, Burtin P. Antiinflammatory immunosuppressants in advanced clinical develpoment for organ transplantation and selected autoimmune diseases. Expert Opin Emerg Drugs 2003; 8(1): 47–62

    PubMed  CAS  Google Scholar 

  9. Mohler KM, Torrance DS, Smith CA, et al. Soluble TNF receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993; 151: 1548–61

    PubMed  CAS  Google Scholar 

  10. Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human TNF receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337: 141–7

    PubMed  CAS  Google Scholar 

  11. Williams RO, Feldmann M, Maini RN. Anti-TNF ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 1992; 89: 9784–8

    PubMed  CAS  Google Scholar 

  12. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 1586–93

    PubMed  CAS  Google Scholar 

  13. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999; 340: 1398–405

    PubMed  CAS  Google Scholar 

  14. Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric mAb cA2 to TNF-alpha for Crohn’s disease: Crohn’s Disease cA2 Study Group. N Engl J Med 1997; 337: 1029–35

    PubMed  CAS  Google Scholar 

  15. D’Haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti-TNF antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology 1999; 116: 1029–34

    PubMed  Google Scholar 

  16. Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-TNF antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 1999; 117: 761–9

    PubMed  CAS  Google Scholar 

  17. Maini RN, Taylor PC. Anti-cytokine therapy for rheumatoid arthritis. Annu Rev Med 2000; 51: 207–29

    PubMed  CAS  Google Scholar 

  18. Kirchner S, Holler E, Haffner S, et al. Effect of different TNF reactive agents on reverse signaling of membrane integrated TNF in monocytes. Cytokine 2004; 28(2): 67–74

    PubMed  CAS  Google Scholar 

  19. Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999; 130: 478–86

    PubMed  CAS  Google Scholar 

  20. Elliott MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric mAbs to TNF-alpha. Arthritis Rheum 1993; 36: 1681–90

    PubMed  CAS  Google Scholar 

  21. Sandborn WJ, Hanauer SB, Katz S, et al. Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2001; 121: 1088–94

    PubMed  CAS  Google Scholar 

  22. Yazdani-Biuki B, Wohlfahrt K, Mulabecirovic A, et al. Long term treatment of psoriatic arthritis with infliximab. Ann Rheum Dis 2004; 63(11): 1531–2

    PubMed  CAS  Google Scholar 

  23. Winterfield L, Menter A. Psoriasis and its treatment with infliximab-mediated TNF-alpha blockade. Dermatol Clin 2004; 22(4): 437–47

    PubMed  CAS  Google Scholar 

  24. Braun J, Sieper J. Biological therapies in the spondyloarthritides: the current state. Rheumatology (Oxford) 2004; 43(9): 1072–84

    CAS  Google Scholar 

  25. Gillett HR, Arnott IDR, McIntyre M, et al. Successful infliximab treatment for steroid-refractory celiac disease: a case report. Gastroenterology 2002; 122: 800–5

    PubMed  Google Scholar 

  26. Holler E, Kolb HJ, Moller A, et al. Increased serum levels of TNF-alpha precede major complications of bone marrow transplantation. Blood 1990; 75: 1011–6

    PubMed  CAS  Google Scholar 

  27. Holler E, Kolb HJ, Mittermuller J, et al. Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by TNF-alpha release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a mAb neutralizing human TNF-alpha (MAK 195F). Blood 1995; 86: 890–9

    PubMed  CAS  Google Scholar 

  28. Remberger M, Ringden O, Markling L. TNF-alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant 1995; 15: 99–104

    PubMed  CAS  Google Scholar 

  29. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. Role of TNF-alpha in acute graft-versus-host disease and complications following allogeneic bone marrow transplantation. Transplant Proc 1993; 25: 1234–6

    PubMed  CAS  Google Scholar 

  30. Herve P, Flesch M, Tiberghien P, et al. Phase I-II trial of a monoclonal anti-TNF-alpha antibody for the treatment of refractory severe acute graft-versus-host disease. Blood 1992; 79: 3362–8

    PubMed  CAS  Google Scholar 

  31. Nagler A, Or R, Nisman B, et al. Elevated inflammatory cytokine levels in bone marrow graft rejection. Transplantation 1995; 60: 943–8

    PubMed  CAS  Google Scholar 

  32. Hill GR, Teshima T, Gerbitz A, et al. Differential roles of IL-1 and TNF-alpha on graft-versus-host and graft versus leukemia. J Clin Invest 1999; 104: 459–67

    PubMed  CAS  Google Scholar 

  33. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 1990; 76: 1464–72

    PubMed  CAS  Google Scholar 

  34. Weisdorf D, Haake R, Blazar B, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990; 75: 1024–30

    PubMed  CAS  Google Scholar 

  35. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host-disease: secondary treatment. Blood 1991; 62: 626–31

    Google Scholar 

  36. Przepiorka D, Kernan NA, Ippoliti C, et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood 2000; 95: 83–9

    PubMed  CAS  Google Scholar 

  37. Brown GR, Lindberg G, Meddings J, et al. TNF inhibitor ameliorates murine intestinal graft-versus-host disease. Gastroenterology 1999; 116: 593–601

    PubMed  CAS  Google Scholar 

  38. Couriel DR, Hicks K, Ippoliti C, et al. Infliximab for the treatment of graft-versus-host disease in allogeneic transplant recipients [abstract no. 200]. Proc Am Soc Clin Oncol 2000; 19: 52a

    Google Scholar 

  39. Pascher A, Radke C, Dignass A, et al. Successful infliximab treatment of steroid and OKT3-refractory acute cellular rejection in two patients after intestinal transplantation. Transplantation 2003; 76(3): 615–8

    PubMed  CAS  Google Scholar 

  40. Azuma H, Nadeau K, Takada M, et al. Cellular and molecular predictors of chronic renal dysfunction after initial ischemia/reperfusion injury of a single kidney. Transplantation 1997; 64: 190–7

    PubMed  CAS  Google Scholar 

  41. Meldrum DR. Tumor necrosis factor in the heart. Am J Physiol 1998; 274: R577–95

    PubMed  CAS  Google Scholar 

  42. Meldrum DR, Dinarello CA, Cleveland JC, et al. Hydrogen peroxide induces tumor necrosis factor alpha-mediated cardiac injury by a p38 mitogen-activated protein kinase-dependent mechanism. Surgery 1998; 124: 291–6

    PubMed  CAS  Google Scholar 

  43. Meldrum DR, Cain BS, Cleveland JC, et al. Adenosine decreases postischemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation. Immunology 1997; 92: 472–7

    PubMed  CAS  Google Scholar 

  44. Meldrum DR, Cleveland JC, Cain BS, et al. Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Ann Thorac Surg 1998; 65: 439–43

    PubMed  CAS  Google Scholar 

  45. Teoh N, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 2003; 18(8): 891–902

    PubMed  CAS  Google Scholar 

  46. Baud L, Oudinet JP, Bens M, et al. Production of tumor necrosis factor by rat mesangial cells in response to bacterial lipopolysaccharide. Kidney Int 1989; 35: 1111–8

    PubMed  CAS  Google Scholar 

  47. Fouqueray B, Philippe C, Herbelin A, et al. Cytokine formation within rat glomeruli during experimental endotoxemia. J Am Soc Nephrol 1993; 3: 1783–91

    PubMed  CAS  Google Scholar 

  48. Kita T, Tanaka N, Nagano T. The immunocytochemical localization of tumor necrosis factor and leukotriene in the rat kidney after treatment with lipopolysaccharide. Int J Exp Path 1993; 74: 471–9

    CAS  Google Scholar 

  49. Wanner GA, Ertel W, Muller P. Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation. Shock 1996; 5: 34–40

    PubMed  CAS  Google Scholar 

  50. Shirasugi N, Wakabayashi G, Shimazu M. Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury. Transplantation 1997; 64: 1398–403

    PubMed  CAS  Google Scholar 

  51. Donnahoo KK, Shames BD, Harken AK, et al. The role of tumor necrosis factor in renal ischemia-reperfusion injury. J Urol 1999; 162: 196–203

    PubMed  CAS  Google Scholar 

  52. Baud L, Perez J, Friedlander G, et al. Tumor necrosis factor stimulates prostaglandin production and cyclic AMP levels in rat cultured mesangial cells. FEBS Lett 1988; 239: 50–4

    PubMed  CAS  Google Scholar 

  53. Gomez-Chiarri M, Ortiz A, Lerma JL, et al. Involvement of tumor necrosis factor and platelet-activating factor in the pathogenesis of experimental nephrosis in rats. Lab Invest 1994; 70: 449–59

    PubMed  CAS  Google Scholar 

  54. Kohan DE. Production of endothelin-1 by rat mesangial cells: regulation by tumor necrosis factor. J Lab Clin Med 1992; 119: 477–84

    PubMed  CAS  Google Scholar 

  55. Savic V, Stefanovic V, Ardaillou N, et al. Induction of ecto-5′-nucleotidase of rat cultured mesangial cells by interleukin-1 beta and tumor necrosis factor-alpha. Immunology 1990; 70: 321–6

    PubMed  CAS  Google Scholar 

  56. Marsden PA, Ballermann BJ. Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism. J Exp Med 1990; 172: 1843–52

    PubMed  CAS  Google Scholar 

  57. Radeke HH, Meier B, Topley N, et al. Interleukin-1 alpha and tumor necrosis factor-alpha induce oxygen radical production in mesangial cells. Kidney Int 1990; 37: 767–75

    PubMed  CAS  Google Scholar 

  58. Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of IL-1. J Exp Med 1986; 163: 1433–50

    PubMed  CAS  Google Scholar 

  59. Manthey CL, Vogel SN. Interactions of lipopolysaccharide with macrophages. Immunol Ser 1994; 60: 63–81

    PubMed  CAS  Google Scholar 

  60. Sweet MJ, Hume DA. Endotoxin signal transduction in macrophages. J Leukoc Biol 1996; 60: 8–26

    PubMed  CAS  Google Scholar 

  61. Lee JD, Kravchenko V, Kirkland TN, et al. GPI-anchored or integral membrane forms of CD14 mediate identical cellular responses to endotoxin. Proc Natl Acad Sci U S A 1993; 90: 9930–4

    PubMed  CAS  Google Scholar 

  62. Han J, Lee JD, Tobias PS, et al. Endotoxin induces rapid tyrosine phosphorylation in 70Z/3 cells expressing CD14. J Biol Chem 1993; 268: 25009–14

    PubMed  CAS  Google Scholar 

  63. Sanghera JS, Weinstein SL, Aluwalia M, et al. Activation of multiple proline-directed kinases by bacterial lipopolysaccharide in murine macrophages. J Immunol 1996; 156: 4457–65

    PubMed  CAS  Google Scholar 

  64. Hsu H, Xiong J, Goeddel DV. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa-B activation. Cell 1995; 81(4): 495–504

    PubMed  CAS  Google Scholar 

  65. Van Aelst L, Barr M, Marcus S, et al. Complex formation between Ras and Raf and other protein kinases. Proc Natl Acad Sci U S A 1993; 90: 6213–7

    PubMed  Google Scholar 

  66. Buscher D, Hipskind RA, Krautwald S, et al. Ras-dependent and independent pathways target the mitogen-activated protein kinase network in macrophages. Mol Cell Biol 1995; 15: 466–75

    PubMed  CAS  Google Scholar 

  67. Han J, Richter B, Li Z, et al. Molecular cloning of the p38 MAP kinase. Biochem Biophys Acta 1995; 1265: 224–7

    PubMed  Google Scholar 

  68. Lee JC, Young PR. Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms. J Leukoc Biol 1996; 59: 152–7

    PubMed  CAS  Google Scholar 

  69. Lee JC, Laydon JT, McDonnell PC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994; 372: 739–46

    PubMed  CAS  Google Scholar 

  70. Pober JS. Activation and injury of endothelial cells by cytokines. Pathol Biol (Paris) 1998; 46(3): 159–63

    CAS  Google Scholar 

  71. Schumer M, Colombel MC, Sawczuk IS, et al. Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Am J Pathol 1992; 140: 831–8

    PubMed  CAS  Google Scholar 

  72. Yin T, Sandhu G, Wolfgang CD, et al. Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney. J Biol Chem 1997; 272: 19943–50

    PubMed  CAS  Google Scholar 

  73. Soler AP, Mullin JM, Knudsen KA, et al. Tissue remodeling during tumor necrosis factor-induced apoptosis in LLC-PK1 renal epithelial cells [abstract]. Am J Physiol 1996; 270: F869

    CAS  Google Scholar 

  74. Chinnaiyan AM, O’Rourke K, Tewari M, et al. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995; 81: 505–12

    PubMed  CAS  Google Scholar 

  75. Boldin MP, Varfolomeev EE, Pancer Z, et al. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem 1995; 270: 7795–8

    PubMed  CAS  Google Scholar 

  76. Cleveland JL, Ihle JN. Contenders in FasL/TNF death signaling. Cell 1995; 81: 479–82

    PubMed  CAS  Google Scholar 

  77. Ohta H, Yatomi Y, Sweeney EA, et al. A possible role of sphingosine in induction of apoptosis by tumor necrosis factor-α in human neutrophils. FEBS Lett 1994; 355: 267–70

    PubMed  CAS  Google Scholar 

  78. Oral HG, Dorn W, Mann DL. Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-α in the adult mammalian cardiac myocyte. J Biol Chem 1997; 272: 4836–42

    PubMed  CAS  Google Scholar 

  79. Sarih M, Souvannavong V, Adam A. Nitric oxide synthase induces macrophage death by apoptosis. Biochem Biophys Res Commun 1993; 191: 503–9

    PubMed  CAS  Google Scholar 

  80. El-Sawy T, Fahmy NM, Fairchild RL. Chemokines: directing leukocyte infiltration into allografts. Curr Opin Immunol 2002; 14(5): 562–8

    PubMed  CAS  Google Scholar 

  81. Yan SF, Fujita T, Lu J, et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med 2000; 6: 1355–61

    PubMed  CAS  Google Scholar 

  82. Naidu BV, Krishnadasan B, Byrne K, et al. Regulation of chemokine expression by cyclosporine A in alveolar macrophages exposed to hypoxia and reoxygenation. Ann Thorac Surg 2002; 74: 899–905

    PubMed  Google Scholar 

  83. Lentsch AB, Yoshidome H, Cheadle WG, et al. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology 1998; 27: 1172–7

    PubMed  CAS  Google Scholar 

  84. Martinez-Mier G, Toledo-Pereyra LH, McDuffie E, et al. L-Selectin and chemokine response after liver ischemia and reperfusion. J Surg Res 2000; 93: 156–62

    PubMed  CAS  Google Scholar 

  85. Kataoka M, Shimizu H, Mitsuhashi N, et al. Effect of cold-ischemia time on c-x-c chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats. Transplantation 2002; 73: 1730–5

    PubMed  CAS  Google Scholar 

  86. Chandrasekar B, Smith JB, Freeman GL. Ischemia reperfusion of rat myocardium activates nuclear factor-B and induces neutrophil infiltration via lipo-polysaccharide-induced cxc chemokine. Circulation 2001; 103: 2296–302

    PubMed  CAS  Google Scholar 

  87. Lakshminarayanan V, Lewallen M, Frangogiannis NG, et al. Reactive oxygen intermediates induce monocyte chemotactic protein-1 in vascular endothelium after brief ischemia. Am J Pathol 2001; 159: 1301–11

    PubMed  CAS  Google Scholar 

  88. Nossuli TO, Frangogiannis NG, Knuefermann P, et al. Brief murine myocardial I/R induces chemokines in a TNF-independent manner: role of oxygen radicals. Am J Physiol Heart Circ Physiol 2001; 281: H2549–58

    PubMed  CAS  Google Scholar 

  89. Heinzelmann M, Mercer-Jones MA, Passmore JC. Neutrophils and renal failure. Am J Kidney Dis 1999; 34: 384–99

    PubMed  CAS  Google Scholar 

  90. Lemay S, Rabb H, Postier G, et al. Prominent and sustained up-regulation of gpl30-signaling cytokines and of the chemokine MIP-2 in murine renal ischemiareperfusion injury. Transplantation 2000; 69: 959–63

    PubMed  CAS  Google Scholar 

  91. Sung FL, Zhu TY, Au-Yeung KK, et al. Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by oxidative stress and NF-B. Kidney Int 2002; 62: 1160–70

    PubMed  CAS  Google Scholar 

  92. Oz MC, Liao H, Naka Y, et al. Ischemia-induced interleukin-8 release after human heart transplantation: a potential role for endothelial cells. Circulation 1995; 92: II428–32

    PubMed  CAS  Google Scholar 

  93. Kumar AG, Ballantyne CM, Michael LH, et al. Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium. Circulation 1997; 95: 693–700

    PubMed  CAS  Google Scholar 

  94. Hancock WW. Chemokine receptor-dependent alloresponses. Immunol Rev 2003; 196: 37–50

    PubMed  CAS  Google Scholar 

  95. Dragun D, Hoff U, Park JK, et al. Prolonged cold preservation augments vascular injury independent of renal transplant immunogenicity and function. Kidney Int 2001; 60: 1173–81

    PubMed  CAS  Google Scholar 

  96. Bergese SD, Huang EH, Pelletier RP, et al. Regulation of endothelial VCAM-1 expression in murine cardiac grafts. Am J Pathol 1995; 147: 166–75

    PubMed  CAS  Google Scholar 

  97. Brennan DC, Jevnikar AM, Takei F, et al. Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1. Kidney Int 1990; 38: 1039–46

    PubMed  CAS  Google Scholar 

  98. Brady HR, Spertini O, Jimenez W, et al. Neutrophils, monocytes, and lymphocytes bind to cytokine-activated kidney glomerular endothelial cells through L-selectin (lam-1) in vitro. J Immunol 1992; 149: 2437–44

    PubMed  CAS  Google Scholar 

  99. Miura M, Fu X, Zhang Q, et al. Neutralization of Gro- and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury. Am J Pathol 2001; 159: 2137–45

    PubMed  CAS  Google Scholar 

  100. Laskowski I, Pratschke J, Wilhelm MJ, et al. Molecular and cellular events associated with ischemia/reperfusion injury. Ann Transplant 2000; 5: 29–35

    PubMed  CAS  Google Scholar 

  101. Smolenski RT, Raisky O, Slominska EM, et al. Protection from reperfusion injury after cardiac transplantation by inhibition of adenosine metabolism and nucleotide precursor supply. Circulation 2001; 104 (12 Suppl. 1): 1246–52

    Google Scholar 

  102. Maury CPJ, Teppo AM. Raised serum levels of cachectin/tumour necrosis factor alpha in renal allograft rejection. J Exp Med 1987; 166: 1132–7

    PubMed  CAS  Google Scholar 

  103. Lowry RP, Biais P. Tumour necrosis factor-alpha in rejecting rat cardiac allografts [abstract]. Transplant Proc 1988; 20: 245

    PubMed  CAS  Google Scholar 

  104. Imagawa DK, Millis JM, Olthoff KM, et al. The role of tumour necrosis factor in allograft rejection: 1. Evidence that elevated levels of tumour necrosis factor-alpha predict rejection following orthotopic liver transplantation. Transplantation 1990; 50: 219–25

    PubMed  CAS  Google Scholar 

  105. Bubnova LN, Kabakov A, Serebrianaya N, et al. Interleukin-1 beta and tumour necrosis factor-alpha serum levels in renal allograft recipients [abstract]. Transplant Proc 1992; 24: 2545

    PubMed  CAS  Google Scholar 

  106. Meulders Q, Rondeau E, Delarue F, et al. TNF-alpha synthesis by circulating mononuclear cells in patients undergoing kidney transplantation [in French]. Presse Med 1991; 20(40): 2001–3

    PubMed  CAS  Google Scholar 

  107. McLaughlin PJ, Aikawa AA, Davies HM, et al. Tumour necrosis factor in renal transplantation. Transplant Proc 1991; 23: 1289–90

    PubMed  CAS  Google Scholar 

  108. Blancho G, Moreau JF, Chabannes D, et al. Human interleukin DA-1a (HILDA)/ LIF, G-CSF, IL-IB, IL-6, and TNF alpha production during acute kidney graft rejection episodes. Transplant Proc 1993; 25: 891–2

    PubMed  CAS  Google Scholar 

  109. Hoffman MW, Wonigeit K, Steinhoff G, et al. Production of cytokines (TNF-alpha, IL-I-beta) and endothelial cell activation in human liver allograft rejection. Transplantation 1993; 55: 329–35

    Google Scholar 

  110. Tilg H, Vogel W, Aulitzky WE, et al. Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation. Transplantation 1990; 49: 1074–80

    PubMed  CAS  Google Scholar 

  111. Imagawa DK, Millis JM, Olthoff KM, et al. The role of tumour necrosis factor in allograft rejection: 2. Evidence that antibody therapy against tumour necrosis factor-alpha and lymphotoxin enhances cardiac allograft survival in rats. Transplantation 1990; 50: 189–93

    PubMed  CAS  Google Scholar 

  112. Grewal HP, Kotb M, Salem A, et al. Elevated tumour necrosis factor levels are predictive for pancreas allograft transplant rejection. Transplant Proc 1993; 25: 132–5

    PubMed  CAS  Google Scholar 

  113. Wiggins MC, Bracher M, Mall A, et al. Tumour necrosis factor levels during acute rejection and acute tubular necrosis in renal transplant recipients. Transpl Immunol 2000 Nov; 8(3): 211–5

    PubMed  CAS  Google Scholar 

  114. Han J, Thompson P, Beutler B. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumour necrosis factor synthesis at separate points in the signaling pathway. J Exp Med 1990; 172: 391–4

    PubMed  CAS  Google Scholar 

  115. Yokoyama I, Todo S, Miyata T, et al. Endotoxemia and human liver transplantation. Transplant Proc 1989; 21: 3833–41

    PubMed  CAS  Google Scholar 

  116. Miyata T, Yokoyama I, Todo S, et al. Endotoxemia, pulmonary complications and thrombocytopenia in liver transplantation. Lancet 1989; II: 189–91

    Google Scholar 

  117. Larsen CP, Morris PJ, Austyn JM. Migration of dendritic leukocytes from cardiac allografts into host spleens: a novel pathway for initiation of rejection. J Exp Med 1990; 171: 307–14

    PubMed  CAS  Google Scholar 

  118. Hancock WW, Wang L, Ye Q. Chemokine-directed dendritic cell trafficking in allograft rejection. Curr Opin Organ Transplant 2003; 8: 35–9

    Google Scholar 

  119. Forster R, Schubel A, Breitfeld D, et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999; 99: 23–33

    PubMed  CAS  Google Scholar 

  120. Gunn MD, Kyuwa S, Tarn C, et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med 1999; 189: 451–60

    PubMed  CAS  Google Scholar 

  121. Gasser M, Waaga AM, Kist-Van Holthe JE, et al. Normalization of brain death-induced injury to rat renal allografts by recombinant soluble P-selectin glycoprotein ligand. J Am Soc Nephrol 2002; 13: 1937–45

    PubMed  CAS  Google Scholar 

  122. Martinez-Mier G, Toledo-Pereyra LH, McDuffie JE, et al. P-Selectin and chemokine response after liver ischemia and reperfusion. J Am Coll Surg 2000; 191: 395–402

    PubMed  CAS  Google Scholar 

  123. Wilhelm MJ, Pratschke J, Beato F, et al. Activation of the heart by donor brain death accelerated acute rejection after transplantation. Circulation 2000; 102: 2426–33

    PubMed  CAS  Google Scholar 

  124. Matzinger P. The danger model: a renewed sense of self. Science 2002; 296: 301–5

    PubMed  CAS  Google Scholar 

  125. Land WG. The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation 2005 Mar 15; 79(5): 505–14

    PubMed  Google Scholar 

  126. Le Moine A, Goldman M, Abramowicz D. Multiple pathways to allograft rejection. Transplantation 2002; 73(9): 1373–81

    PubMed  Google Scholar 

  127. Zelenika D, Adams E, Mellor A, et al. Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: no requirement for CD8+ T cells or B cells. J Immunol 1998; 161: 1868–74

    PubMed  CAS  Google Scholar 

  128. Valujskikh A, Matesic D, Gilliam A, et al. T cells reactive to a single immunodominant self-restricted allopeptide induce skin graft rejection in mice. J Clin Invest 1998; 101: 1398–407

    PubMed  CAS  Google Scholar 

  129. Dalloul AH, Chmouzis E, Ngo K, et al. Adoptively transferred CD4+ lymphocytes from CD8−/− mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts. J Immunol 1996; 156: 4114–9

    PubMed  CAS  Google Scholar 

  130. Grimm PC, McKenna R, Nickerson P, et al. Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages. J Am Soc Nephrol 1999; 10: 1582–9

    PubMed  CAS  Google Scholar 

  131. Worrall NK, Lazenby WD, Misko TP, et al. Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase. J Exp Med 1995; 181: 63–70

    PubMed  CAS  Google Scholar 

  132. Braun MY, Grandjean I, Feunou P, et al. Acute rejection in the absence of cognate recognition of allograft by T cells. J Immunol 2001; 166: 4879–83

    PubMed  CAS  Google Scholar 

  133. Sandborn WJ. New concepts in anti-tumor necrosis factor therapy for inflammatory bowel disease. Rev Gastroenterol Disord 2005; 5(1): 10–8

    PubMed  Google Scholar 

  134. Alho HS, Maasilta PK, Harjula AL, et al. TNF-alpha in a porcine bronchial model of obliterative bronchiolitis. Transplantation 2003; 76(3): 516–23

    PubMed  CAS  Google Scholar 

  135. Fishbein TM. The current state of intestinal transplantation. Transplantation 2004; 78(2): 175–8

    PubMed  Google Scholar 

  136. Vincenti F. New mAbs in renal transplantation. Minerva Urol Nefrol 2003; 55(1): 57–66

    PubMed  CAS  Google Scholar 

  137. Pratschke J, Fehlberg J, Kordic M, et al. Protective and adverse effects of perioperative TNF-alpha blockade in experimental kidney transplantation with living and brain-dead donor grafts. Am J Transplant 2003; 3 Suppl.: 949

    Google Scholar 

  138. Eason JD, Wee S, Kawai T, et al. Inhibition of the effects of TNF in renal allograft recipients using recombinant human dimeric TNF receptors. Transplantation 1995; 59(2): 300–5

    PubMed  CAS  Google Scholar 

  139. Langrehr JM, Hammer MH, Gube K, et al. Short-term anti-CD4 plus anti-TNF alpha receptor treatment in allogeneic small bowel transplantation results in long-term allograft survival. Am J Transplant 2004; 4Suppl. 8: 430

    Google Scholar 

  140. Smith CR, Jaramillo A, Lu KC, et al. Prevention of obliterative airway disease in HLA-A2-transgenic tracheal allografts by neutralization of TNF. Transplantation 2001; 72(9): 1512–8

    PubMed  CAS  Google Scholar 

  141. Smith C, Jaramillo A, Lu KC, et al. Neutralization of TNF-alpha or interleukin-1 prevents obliterative airway disease in HLA-A2 transgenic murine tracheal allografts. J Heart Lung Transplant 2001; 20(2): 166–7

    PubMed  Google Scholar 

  142. Hering BJ, Kandaswamy R, Ansite JD, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 2005; 293(7): 830–5

    PubMed  CAS  Google Scholar 

  143. Hanauer S, Lukas M, MacIntosh D, et al. A randomized, double-blind, placebo-controlled trial of the human anti-TNF-monoclonal antibody adalimumab for the induction of remission in patients with moderate to severely active Crohn’s disease [abstract]. Gastroenterology 2004; 127: 332

    Google Scholar 

  144. Sandborn WJ, Hanauer S, Loftus EV, et al. An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. Am J Gastroenterol 2004; 99: 1984–9

    PubMed  CAS  Google Scholar 

  145. Schreiber S, Rutgeerts P, Fedorak R, et al. CDP870, a humanized anti-TNF antibody fragment, induces clinical response with remission in patients with active Crohn’s disease (CD): the CDP870 Crohn’s Disease Study Group. Gastroenterology 2003; 124: A–61

    Google Scholar 

  146. Winter T, Wright J, Ghosh S, et al. Intravenous CDP870, a humanized anti-TNF antibody fragment, in patients with active Crohn’s disease: an exploratory study. Gastroenterology 2003; 124: A–377

    Google Scholar 

  147. Stack WA, Mann SD, Roy AJ, et al. Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn’s disease. Lancet 1997; 349: 521–4

    PubMed  CAS  Google Scholar 

  148. Sandborn WJ, Feagan BG, Hanauer SB, et al. An engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized double-blind placebo-controlled trial. Gastroenterology 2001; 120: 1330–8

    PubMed  CAS  Google Scholar 

  149. Sandborn WJ, Feagan BG, Radford-Smith G, et al. CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn’s disease: a randomised, double-blind, placebo-controlled trial. Gut 2004; 53: 1485–93

    PubMed  CAS  Google Scholar 

  150. Feagan BG, Sandborn WJ, Baker J, et al. A randomized, double-blind, placebo-controlled, multicenter trial of the engineered human antibody to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroid-dependent Crohn’s disease [abstract]. Gastroenterology 2000; 118: A655

    Google Scholar 

  151. Celltech announces results from CDP 571 phase III studies in Crohn’s disease [press release]. Berkshire, UK: Celltech Group plc, 2002 Jul 30

  152. Hanauer S, Present D, Targan SR, et al. CDP571, a humanized monoclonal antibody to TNF-, is well tolerated in Crohn’s disease patients with previous hypersensitivity to infliximab. Gastroenterology 2003; 124: A–517

    Google Scholar 

  153. Rutgeerts P, Fedorak RN, Rachmilevich D, et al. Onercept (recombinant human p55 tumour necrosis factor receptor) treatment in patients with active Crohn’s disease: randomized, placebo-controlled, dose-finding phase II study. The Onercept Study Group T. Gut 2004; 53Suppl. VI: A47

    Google Scholar 

  154. Rutgeerts P, Lemmens L, Van Assche G, et al. Treatment of active Crohn’s disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study. Aliment Pharmacol Ther 2003; 17: 185–92

    PubMed  CAS  Google Scholar 

  155. Rudiger HA, Clavien PA. TNF-alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. Gastroenterology 2002; 122(1): 202–10

    PubMed  CAS  Google Scholar 

  156. Selzner N, Selzner M, Tian Y, et al. Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: a TNF-alpha/IL-6-dependent mechanism. Hepatology 2002; 36 (4 Pt 1): 812–8

    PubMed  CAS  Google Scholar 

  157. Nishizawa H, Egawa H, Inomata Y, et al. Efficiency of pentoxifyllinee in donor pretreatment in rat liver transplantation. J Surg Res 1997; 72(2): 170–6

    PubMed  CAS  Google Scholar 

  158. Astarcioglu H, Karademir S, Unek T, et al. Beneficial effects of pentoxifyllinee pretreatment in non-heart-beating donors in rats. Transplantation 2000; 69(1): 93–8

    PubMed  CAS  Google Scholar 

  159. Kozaki K, Egawa H, Bermudez L, et al. Effects of pentoxifyllinee pretreatment on Kupffer cells in rat liver transplantation. Hepatology 1995; 21(4): 1079–82

    PubMed  CAS  Google Scholar 

  160. Peng XX, Currin RT, Thurman RG, et al. Protection by pentoxifyllinee against normothermic liver IR in rats. Transplantation 1995; 59(11): 1537–41

    PubMed  CAS  Google Scholar 

  161. Ben-Ari Z, Hochhauser E, Burstein I, et al. Role of anti-TNF-alpha in IR injury in isolated rat liver in a blood-free environment. Transplantation 2002; 73(12): 1875–80

    PubMed  CAS  Google Scholar 

  162. Imagawa DK, Millis JM, Olthoff KM, et al. Anti-TNF antibody enhances allograft survival in rats. J Surg Res 1990; 48(4): 345–8

    PubMed  CAS  Google Scholar 

  163. Platz KP, Mueller AR, Rossaint R, et al. Cytokine pattern during rejection and infection after liver transplantation-improvements in postoperative monitoring? Transplantation 1996; 62(10): 1441–50

    PubMed  CAS  Google Scholar 

  164. Bathgate AJ, Lee P, Hayes PC, et al. Pretransplantation TNF-alpha production predicts acute rejection after liver transplantation. Liver Transpl 2000; 6(6): 721–7

    PubMed  CAS  Google Scholar 

  165. Daemen MA, van de Ven MW, Heineman E, et al. Involvement of endogenous interleukin-10 and TNF-alpha in renal IR injury. Transplantation 1999; 67(6): 792–800

    PubMed  CAS  Google Scholar 

  166. Donnahoo KK, Meng X, Ayala A, et al. Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal IR. Am J Physiol 1999; 277 (3 Pt 2): R922–9

    PubMed  CAS  Google Scholar 

  167. Donnahoo KK, Meng X, Ao L, et al. Differential cellular immunolocalization of renal tumour necrosis factor-alpha production during ischaemia versus endotoxaemia. Immunology 2001; 102(1): 53–8

    PubMed  CAS  Google Scholar 

  168. Kim YK, Yoo JH, Woo JS, et al. Effect of pentoxifylline on ischemic acute renal failure in rabbits. Ren Fail 2001; 23(6): 757–72

    PubMed  CAS  Google Scholar 

  169. Abu-Elmagd K, Fung J, McGhee W, et al. The efficacy of daclizumab for intestinal transplantation: preliminary report. Transplant Proc 2000; 32: 1195–6

    PubMed  CAS  Google Scholar 

  170. Abu-Elmagd K, Reyes J, Bond G, et al. Clinical intestinal transplantation: a decade of experience at a single center. Ann Surg 2001; 234: 404–16

    PubMed  CAS  Google Scholar 

  171. Fishbein TM, Florman S, Gondolesi G, et al. Intestinal transplantation before and after introduction of sirolimus. Transplantation 2002; 73: 1538–42

    PubMed  CAS  Google Scholar 

  172. McDiarmid SV, Farmer DG, Kuniyoshi JS, et al. The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. Transplantation 1994; 58(6): 690–7

    PubMed  CAS  Google Scholar 

  173. Farmer DG, McDiarmid SV, Kuniyoshi J, et al. Intragraft expression of messenger RNA for interleukin-6 and TNF-alpha is a predictor of rat small intestine transplant rejection. J Surg Res 1994; 57(1): 138–42

    PubMed  CAS  Google Scholar 

  174. Mueller AR, Platz KP, Heckert C, et al. The extracellular matrix: an early target of preservation/reperfusion injury and acute rejection after small bowel transplantation. Transplantation 1998; 65(6): 770–6

    PubMed  CAS  Google Scholar 

  175. Kobbe G, Schneider P, Rohr U, et al. Treatment of severe steroid refractory acute GvHD with infliximab, a chimeric human/mouse anti TNFalpha antibody. Bone Marrow Transplant 2001; 28: 47–9

    PubMed  CAS  Google Scholar 

  176. Pascher A, Klupp J, Langrehr JM, et al. Anti-TNF-α therapy for acute rejection in intestinal transplantation. Transplant Proc 2005; 37(3): 1635–6

    PubMed  CAS  Google Scholar 

  177. Azzawi M, Hasleton P. Tumour necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease. Cardiovasc Res 1999; 43: 850–9

    PubMed  CAS  Google Scholar 

  178. Bellisarii FL, Gallina S, De Caterina R. Tumor necrosis factor-alpha and cardiovascular diseases. Ital Heart J 2001; 2: 408–17

    PubMed  CAS  Google Scholar 

  179. Frangogiannis NG, Lindsey ML, Michael LH, et al. Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 1998; 98: 699–710

    PubMed  CAS  Google Scholar 

  180. Gurevitch J, Frolkis I, Yuhas Y, et al. Tumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion. J Am Coll Cardiol 1996; 28: 247–52

    PubMed  CAS  Google Scholar 

  181. Irwin MW, Mak S, Mann DL, et al. Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium. Circulation 1999; 99: 1492–8

    PubMed  CAS  Google Scholar 

  182. Dörge H, Schulz R, Belosjorow S, et al. Coronary microembolization: the role of TNFα in contractile dysfunction. J Mol Cell Cardiol 2002; 34: 51–62

    PubMed  Google Scholar 

  183. Kapadia S, Oral H, Lee J, et al. Hemodynamic regulation of tumor necrosis factor alpha-gene and protein expression in adult feline myocardium. Circ Res 1997; 81: 187–95

    PubMed  CAS  Google Scholar 

  184. Ono K, Matsumori A, Shioi T, et al. Cytokine gene expression after myocardial infarction in rat hearts. Circulation 1998; 98: 149–56

    PubMed  CAS  Google Scholar 

  185. Thielmann M, Dörge H, Martin C, et al. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha and sphingosine. Circ Res 2002; 90: 807–13

    PubMed  CAS  Google Scholar 

  186. Gurevitch J, Frolkis I, Yuhas Y, et al. Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. J Am Coll Cardiol 1997; 30: 1554–61

    PubMed  CAS  Google Scholar 

  187. Belosjorow S, Bolle I, Duschin A, et al. TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits. Am J Physiol Heart Circ Physiol 2003; 284: H927–30

    PubMed  CAS  Google Scholar 

  188. Li D, Zhao L, Liu M, et al. Kinetics of tumor necrosis factor alpha in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor alpha in acute myocardial infarction. Am Heart J 1999; 137: 1145–52

    PubMed  CAS  Google Scholar 

  189. Maekawa N, Wada H, Kanda T, et al. Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-alpha. J Am Coll Cardiol 2002; 39: 1229–35

    PubMed  CAS  Google Scholar 

  190. Schulz R, Aker S, Belosjorow S, et al. TNF alpha in ischemia/reperfusion injury and heart failure. Basic Res Cardiol 2004; 99: 8–11

    PubMed  CAS  Google Scholar 

  191. Chung ES, Packer M, Hung K, et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure. Circulation 2003; 107: 3133–40

    PubMed  CAS  Google Scholar 

  192. Chollet-Martin S, Depoix JP, Hvass Y, et al. Raised plasma levels TNF in heart allograft rejection. Transplant Proc 1990; 22: 283–5

    PubMed  CAS  Google Scholar 

  193. Imagawa DK, Millis JM, Seu P, et al. The role of TNF in allograft rejection: III. Evidence that anti-TNF antibody therapy prolongs allograft survival in rats with acute rejection. Transplantation 1991; 51(1): 57–62

    PubMed  CAS  Google Scholar 

  194. Lin H, Chensue SW, Strieter RM, et al. Antibodies against TNF prolong cardiac allograft survival in the rat. J Heart Lung Transplant 1992; 11 (2 Pt 1): 330–5

    PubMed  CAS  Google Scholar 

  195. Boiling SF, Kunkel SL, Lin H. Prolongation of cardiac allograft survival in rats by anti-TNF and cyclosporine combination therapy. Transplantation 1992; 53(2): 283–6

    Google Scholar 

  196. Wei RQ, Lin H, Chen GH, et al. Inhibition of TNF production by lymphocytes from anti-TNF antibody-treated, cardiac-allografted rats. J Surg Res 1994; 56(6): 601–5

    PubMed  CAS  Google Scholar 

  197. Wei RQ, Schwartz CF, Lin H, et al. Anti-TNF antibody modulates cytokine and MHC expression in cardiac allografts. J Surg Res 1999; 81(2): 123–8

    PubMed  CAS  Google Scholar 

  198. Coito AJ, Binder J, Brown LF, et al. Anti-TNF-alpha treatment down-regulates the expression of fibronectin and decreases cellular infiltration of cardiac allografts in rats. J Immunol 1995; 154(6): 2949–58

    PubMed  CAS  Google Scholar 

  199. Gerber DA, Oettinger CW, D’Souza M, et al. Prolongation of murine cardiac allograft survival by microspheres containing TNF-alpha and IL1-beta neutralizing antibodies. J Drug Target 1995; 3(4): 311–5

    PubMed  CAS  Google Scholar 

  200. Arbustini E, Grasso M, Diegole M, et al. Expression of tumor necrosis factor in human acute cardiac rejection: an immunohistochemical and immunoblotting study. Am J Pathol 1991; 139: 709–15

    PubMed  CAS  Google Scholar 

  201. Mclaughlin PJ, Aikawa A, Davies HM, et al. Evaluation of sequential plasma and urinary tumour necrosis factor levels in renal allograft recipients. Transplantation 1991; 51: 1225–8

    PubMed  CAS  Google Scholar 

  202. Jordan SC, Czer L, Toyoda M, et al. Serum cytokine levels in heart allograft recipients: correlation with findings on endomyocardial biopsy. J Heart Lung Transplant 1993; 12: 333–7

    PubMed  CAS  Google Scholar 

  203. Abdallah AN, Billes MA, Attia Y, et al. Evaluation of plasma levels of tumor necrosis factor alpha and interleukin-6 as rejection markers in a cohort of 142 heart-grafted patients followed by endomyocardial biopsy. Eur Heart J 1997; 18: 1024–9

    PubMed  CAS  Google Scholar 

  204. Azzawi M, Grant SD, Hasleton PS, et al. TNF-alpha mRNA and protein in cardiac transplant biopsies: comparison with serum TNF-alpha levels. Cardiovasc Res 1996; 32(3): 551–6

    PubMed  CAS  Google Scholar 

  205. Azzawi M, Hasleton PS, Hutchinson IV. TNF-alpha in acute cardiac transplant rejection. Cytokines Cell Mol Ther 1999; 5(1): 41–9

    PubMed  CAS  Google Scholar 

  206. Azzawi M, Hasleton PS, Turner DM, et al. TNF-alpha gene polymorphism and death due to acute cellular rejection in a subgroup of heart transplant recipients. Hum Immunol 2001 Feb; 62(2): 140–2

    PubMed  CAS  Google Scholar 

  207. Chapelier A, Reignier J, Mazmanian M, et al. Amelioration of reperfusion injury by pentoxifylline after lung transplantation: the Universite Paris-Sud Lung Transplant Group. J Heart Lung Transplant 1995; 14(4): 676–83

    PubMed  CAS  Google Scholar 

  208. Chapelier A, Reignier J, Mazmanian M, et al. Pentoxifylline and lung IR injury: application to lung transplantation. J Cardiovasc Pharmacol 1995; 25Suppl. 2: S130–3

    PubMed  CAS  Google Scholar 

  209. Reignier J, Mazmanian M, Detruit H, et al. Reduction of IR injury by pentoxifylline in the isolated rat lung. Am J Respir Crit Care Med 1994; 150(2): 342–7

    PubMed  CAS  Google Scholar 

  210. Yamashita M, Schmid RA, Okabayashi K, et al. Pentoxifylline in flush solution improves early lung allograft function. Ann Thorac Surg 1996; 61(4): 1055–61

    PubMed  CAS  Google Scholar 

  211. Okabayashi K, Aoe M, DeMeester SR, et al. Pentoxifylline reduces lung allograft reperfusion injury. Ann Thorac Surg 1994; 58(1): 50–6

    PubMed  CAS  Google Scholar 

  212. Chiang CH, Wu CP, Perng WC, et al. Use of anti- (tumour necrosis factor-alpha) antibody or 3-deaza-adenosine as additives to promote protection by University of Wisconsin solution in ischaemia/reperfusion injury. Clin Sci (Lond) 2000; 99(3): 215–22

    CAS  Google Scholar 

  213. Tagawa T, Kozower BD, Kanaan SA, et al. TNF inhibitor gene transfer ameliorates lung graft IR injury. J Thorac Cardiovasc Surg 2003; 126(4): 1147–54

    PubMed  CAS  Google Scholar 

  214. Tagawa T, Kozower BD, Kanaan SA, et al. Gene transfer of TNF inhibitor improves the function of lung allografts. J Thorac Cardiovasc Surg 2004; 127(6): 1558–63

    PubMed  CAS  Google Scholar 

  215. Aris RM, Walsh S, Chalermskulrat W, et al. Growth factor upregulation during obliterative bronchiolitis in the mouse model. Am J Respir Crit Care Med 2002; 166(3): 417–22

    PubMed  Google Scholar 

  216. Abendroth D, Storck M, Techt B, et al. Analysis of the rejection markers TNF, ICAM-1, neopterin, interleukin-10, and soluble HLA in simultaneous pancreas and kidney transplantation with bladder drainage. Transplant Proc 1995; 27(6): 3114–5

    PubMed  CAS  Google Scholar 

  217. Pelletier R, Pravica V, Perrey C, et al. Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation. Transplantation 2000; 70(4): 674–80

    PubMed  CAS  Google Scholar 

  218. Remicade™, infliximab [product information]. Malvern (PA): Centocor Inc, 1999

  219. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541–9

    PubMed  CAS  Google Scholar 

  220. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350: 876–85

    PubMed  CAS  Google Scholar 

  221. Remicade™ (infliximab) for IV injection. Prescribing information 2005 [online]. Available from URL: httpV/www.remicade.com/pdf/HCP-PPI.pdf [Accessed 2005 Jun 20]

  222. Hanauer SB, Wagner CL, Bala M, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2004; 2: 542–53

    PubMed  CAS  Google Scholar 

  223. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 2003; 348: 601–8

    PubMed  CAS  Google Scholar 

  224. Farrell RJ, Alsahli M, Jeen YT, et al. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 2003; 124: 917–24

    PubMed  CAS  Google Scholar 

  225. Sandborn WJ, Hanauer S, Loftus EV, et al. An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. Am J Gastroenterol 2004; 99: 1984–9

    PubMed  CAS  Google Scholar 

  226. Humira™ (package insert) [online]. Abbott Park (IL): Abbott Laboratories, 2005. Available from URL: http://www.rxabott.com/pdf/humira.pdf [Accessed 2005 Jun 20]

  227. Sandborn WJ, Feagan BG, Radford-Smith G, et al. CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn’s disease: a randomised, double-blind, placebo-controlled trial. Gut 2004; 53: 1485–93

    PubMed  CAS  Google Scholar 

  228. Hanauer S, Rutgeerts P, Targan S, et al. Delayed hypersensitivity to infliximab (Remicade) reinfusion after a 2–4 year interval without treatment [abstract]. Gastroenterology 1999; 116: A731

    Google Scholar 

  229. Vermeire S, Noman M, Van Assche G, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn’s disease: a prospective cohort study. Gastroenterology 2003; 125: 32–9

    PubMed  CAS  Google Scholar 

  230. Kwon HJ, Cote TR, Cuffe MS, et al. Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med 2003; 138: 807–11

    PubMed  Google Scholar 

  231. Antoni C, Braun J. Side effects of anti-TNF therapy: current knowledge. Clin Exp Rheumatol 2002; 20 (6 Suppl. 28): S152–7

    PubMed  CAS  Google Scholar 

  232. Mohan N, Edwards ET, Cupps TR, et al. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001; 44: 2862–9

    PubMed  CAS  Google Scholar 

  233. Thomas CW, Weinshenker BG, Sandborn WJ. Demyelination during anti-tumor necrosis factor alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004; 10: 28–31

    PubMed  Google Scholar 

  234. Brown SL, Greene MH, Gershon SK, et al. Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 2002; 46: 3151–8

    PubMed  CAS  Google Scholar 

  235. Markham A, Lamb HM. Infliximab: a review of its use in the management of rheumatoid arthritis. Drugs 2000; 59: 1341–59

    PubMed  CAS  Google Scholar 

  236. Fisher CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor Fc fusion protein. N Engl J Med 1996; 334: 1697–702

    PubMed  CAS  Google Scholar 

  237. Keane J, Gershon S, Wise YRP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345: 1098–104

    PubMed  CAS  Google Scholar 

  238. Lee JH, Slifman NR, Gershon SK, et al. Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arthritis Rheum 2002; 46: 2565–70

    PubMed  CAS  Google Scholar 

  239. De Rosa FG, Shaz D, Campagna AC, et al. Invasive pulmonary aspergillosis soon after therapy with infliximab, a tumor necrosis factor-alpha-neutralizing antibody: a possible healthcare-associated case? Infect Control Hosp Epidemiol 2003; 24(7): 477–82

    PubMed  Google Scholar 

  240. Velayos FS, Sandborn WJ. Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004; 10: 1657–60

    Google Scholar 

  241. Keenan GF, Schaible TF, Boscia JA. Invasive pulmonary aspergillosis associated with infliximab therapy [letter]. N Engl J Med 2001; 344: 1100

    Google Scholar 

  242. Warris A, Bjorneklett A, Gaustad P. Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med 2001; 344: 1099–100

    PubMed  CAS  Google Scholar 

  243. Latge JP. The pathobiology of Aspergillus fumigatus. Trends Microbiol 2001; 9: 382–9

    PubMed  CAS  Google Scholar 

  244. Pierik M, Vermeire S, Steen KV, et al. Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment Pharmacol Ther 2004; 20(3): 303–10

    PubMed  CAS  Google Scholar 

  245. Louis E, El Ghoul Z, Vermeire S, et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn’s disease. Aliment Pharmacol Ther 2004; 19(5): 511–9

    PubMed  CAS  Google Scholar 

  246. Cuchacovich M, Ferreira L, Aliste M, et al. Tumour necrosis factor-alpha (TNF-alpha) levels and influence of −308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis. Scand J Rheumatol 2004; 33(4): 228–32

    PubMed  CAS  Google Scholar 

  247. Mugnier B, Balandraud N, Darque A, et al. Polymorphism at position −308 of the TNF-alpha gene influences outcome of infliximab therapy in rheumatoid arthritis. Arthritis Rheum 2003; 48(7): 1849–52

    PubMed  CAS  Google Scholar 

  248. Louis E, Vermeire S, Rutgeerts P, et al. A positive response to infliximab in Crohn’s disease: association with a higher systemic inflammation before treatment but not with −308 TNF gene polymorphism. Scand J Gastroenterol 2002; 37(7): 818–24

    PubMed  CAS  Google Scholar 

  249. Taylor KD, Plevy SE, Yang H, et al. ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn’s disease. Gastroenterology 2001; 120(6): 1347–55

    PubMed  CAS  Google Scholar 

  250. Su C, Lichtenstein GR. Are there predictors of Remicade treatment success or failure? Adv Drug Deliv Rev 2005; 57(2): 237–45

    PubMed  CAS  Google Scholar 

  251. Poli F, Boschiero L, Giannoni F, et al. Tumour necrosis factor-alpha gene polymorphism: implications in kidney transplantation. Cytokine 2000; 12: 1778–83

    PubMed  CAS  Google Scholar 

  252. Vincenti F, Pace D, Birnbaum J, et al. Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation. Am J Transplant 2003; 3(1): 50–2

    PubMed  CAS  Google Scholar 

  253. Pascher A, Sauer IM, Schulz RJ, et al. Monitoring of immunosuppression after clinical small bowel transplantation. Transplant Proc 2002; 34: 931–3

    PubMed  CAS  Google Scholar 

  254. Klupp J, van Gelder T, Dambrin C, et al. Sustained suppression of peripheral blood immune functions by treatment with mycophenolate mofetil correlates with reduced severity of cardiac allograft rejection. J Heart Lung Transplant 2004; 23(3): 334–51

    PubMed  Google Scholar 

  255. Gearing AJ, Beckett P, Christodoulou M, et al. Processing of tumor necrosis factor-alpha precursor by metalloproteinases. Nature 1994; 370: 555–7

    PubMed  CAS  Google Scholar 

  256. McGeehan GM, Becherer JD, Bast R, et al. Regulation of TNF-alpha processing by a metalloproteinase inhibitor. Nature 1994; 370: 558–61

    PubMed  CAS  Google Scholar 

  257. Mohler KM, Sleath PR, Fitzner JN, et al. Protection against a lethal dose of endotoxin by an inhibitor of TNF processing. Nature 1994; 370: 218–20

    PubMed  CAS  Google Scholar 

  258. Dinarello CA, Margolis NH. Cytokine-processing enzymes: stopping the cuts. Curr Biol 1995; 5: 587–90

    PubMed  CAS  Google Scholar 

  259. Cleveland JC, Wolmering M, Meldrum DR, et al. Ischemic preconditioning in human and rat ventricle. Am J Physiol 1996; 271 (5 Pt 2): H1786–94

    PubMed  CAS  Google Scholar 

  260. Buchman TG. Manipulation of stress gene expression: a novel therapy for the treatment of sepsis? Crit Care Med 1994; 22: 901–3

    PubMed  CAS  Google Scholar 

  261. Rowland RT, Cleveland JC, Meng X, et al. Potential gene therapy strategies in the treatment of cardiovascular disease. Ann Thorac Surg 1995; 60: 721–8

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors declare that there are no conflicts of interest, in particular no financial funding, potentially relevant to the contents of the manuscript.

Author information

Authors and Affiliations

  1. Department of Visceral and Transplantation Surgery, Universitaetsmedizin Berlin-Charité, Campus Virchow Klinikum, Augustenburgerplatz 1, Berlin, 13353, Germany

    Andreas Pascher & Jochen Klupp

Authors
  1. Andreas Pascher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jochen Klupp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Pascher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pascher, A., Klupp, J. Biologics in the Treatment of Transplant Rejection and Ischemia/Reperfusion Injury. BioDrugs 19, 211–231 (2005). https://doi.org/10.2165/00063030-200519040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200519040-00002

Keywords

Search

Navigation