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Anti-Inflammatory Cytokines: Role in Regulation of Acute Lung Injury

  • Thomas P. Shanley
Chapter
  • 86 Downloads
Part of the Molecular and Cellular Biology of Critical Care Medicine book series (MCCM, volume 1)

Abstract

The concept of balance has been appreciated in the physical sciences for centuries. In the early study of inflammation, attention was focussed primarily on molecules categorized as proinflammatory (e.g. TNF) by virtue of the role they played in mediating leukocyte recruitment, endothelial damage, and tissue injury in critical illness. It was concluded that clinical states such as acute lung injury (ALI) and sepsis were a reflection of an overwhelming proinflammatory state of the host. Over the past decade, investigators have observed that at times the host is able to control or regulate the initial proinflammatory response resulting from activation of innate immune mechanisms. This response confers containment of the inflammation and is thought to afford protection from tissue injury and perhaps, hasten resolution. In the setting of the systemic inflammatory response syndrome (SIRS), this compensatory response was assigned the acronym CARS, or compensatory anti-inflammatory response syndrome (1). Perturbation of this response by exogenous factors, such as pathogens, or endogenous factors, such as genetic regulation of anti-inflammatory cytokine expression, can have important consequences on host survival.

Keywords

Lung Injury Acute Lung Injury Systemic Inflammatory Response Syndrome Leukemia Inhibitory Factor Lung Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Bone, R.C. (1996) Sir Isaac Newton, sepsis, SIRS and CARS. Crit Care Med 24, 1125–1128PubMedCrossRefGoogle Scholar
  2. 2.
    Fiorentino, D.F., Bond, M.W., and Mosmann, T.R. (1989) Two types of mouse T helper cells IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170, 2081–2095PubMedCrossRefGoogle Scholar
  3. 3.
    Vieira, P., de Waal-Malefyt, R., Dang, M.N., Johnson, K.E., Kastelein, R., Fiorentino, D.F., deVries, J.E., Roncarolo, M.G., Mosmann, T.R., and Moore K.W. (1991) Isolation and expression of human cytokine synthesis inhibitory factor (CSIF.IL-10) cDNA clones: homology to Epstein Barr virus opening reading frame. Proc Natl Acad Sci USA 88, 1172–1176PubMedCrossRefGoogle Scholar
  4. 4.
    de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C.G., and de Vries, J.E. (1991) Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes: an auto-regulatory role of IL-10 produced by monocytes. J Exp Med 174, 1209–1220PubMedCrossRefGoogle Scholar
  5. 5.
    Howard, M., and O’Garra, A. (1992) Biological properties of interleukin-10. Immunol Today 13, 198–200PubMedCrossRefGoogle Scholar
  6. 6.
    Moore, K.W., de Waal Malefyt, R., Coffman, R.L., and O’Garra, A. (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19, 683–765PubMedCrossRefGoogle Scholar
  7. 7.
    Opal, S.M., and DePalo, V.A. (2000) Anti-inflammatory cytokines. Chest 117, 1162–1172PubMedCrossRefGoogle Scholar
  8. 8.
    Cassatella, M.A., Meda, L., Gasperini, S., Calzetti, F., and Bonora, S. (1994) Interleukin-10 (IL-10) upregulates IL-1 receptor antagonist production from lipopoly-saccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 179, 1695–1699PubMedCrossRefGoogle Scholar
  9. 9.
    Dickensheets, H.L., Freeman, S.L., Smith, M.F. and Donnelly, R.P. (1994) Interleukin-10 upregulates tumor necrosis factor receptor type II (p75) gene expression in endotoxin-stimulated human monocytes. Blood 90, 4162–4171Google Scholar
  10. 10.
    Tone, M., Powell, M.J., Tone, Y., Thompson, S.A.J., and Waldmann, H. (2000) IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3. J Immunol 165, 286–291PubMedGoogle Scholar
  11. 11.
    Powell, M.J., Thompson, S.A.J., Tone, Y., Waldmann, H., Tone, M. (2000) Post-transcriptional regulation of IL-10 gene expression through sequences in the 3′-untranslated region. J Immunol 165, 292–296PubMedGoogle Scholar
  12. 12.
    Kotenko, S.V., Krause, C.D., Izotova, L.S., Pollack, B.P., Wu, W., and Pestka, S. (1997) Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J 16, 5894–5903PubMedCrossRefGoogle Scholar
  13. 13.
    Hou, J., Schindler, U., Henzel, W.J., Ho, T.C., Brasseur, M., and McKnight, S.L. (1994) An interleukin-4-induced transcription factor: IL-4 Stat. Science 265, 1701–1706PubMedCrossRefGoogle Scholar
  14. 14.
    Finbloom D.S., and Winestock, K.D. (1995) IL-10 induces the tyrosine phosphorylation of tyk2 and Jakl and the differential assembly of Stat-1α and Stat3 complexes in human T-cells and monocytes. J Immunol 155, 1079–1090PubMedGoogle Scholar
  15. 15.
    Riley, J.K., Takeda, K., Akira, S., and Schreiber, R.D. (1990) Interleukin-10 receptor signaling through the JAK-STAT pathway. J Immunol 155, 1079–1090Google Scholar
  16. 16.
    Weber-Nordt R.M., Riley J.K., Greenlund A.C., Moore K.W., Darnell J.E., and Schreiber, R.D. (1996) Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J Biol Chem 271, 27954–27961PubMedCrossRefGoogle Scholar
  17. 17.
    Takeda, K., Clausen, B.E., Kaisho, T., Tsujimura, T., Terada, N., Forster, I., and Akira, S. (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39–49PubMedCrossRefGoogle Scholar
  18. 18.
    Ito, S., Ansari, P., Sakatsume, M., Dickensheets, H., Vazquex, N., Donnelley, R.P., Larner, A.C., and Finbloom, D.S. (1999) Interleukin-10 inhibits expression of both interferon α- and interferon γ-induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 93, 1456–1463PubMedGoogle Scholar
  19. 19.
    Cassatella, M.A., Gasperini, S., Bovolenta, C., Calzetti, F., Vollebregt, M., Scapini, P., Marchi, M., Suzuki, R., Suzuki, A., and Yoshimura, A. (1999) Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: evidence for an IL-10-induced pathway that is independent of STAT protein activation. J Interferon Cytokine Res 19, 679–685CrossRefGoogle Scholar
  20. 20.
    Geng, Y., Gulbins, E., Altman, A., and Lotz, M. (1994) Monocyte deactivation by interleukin-10 via inhibition of tyrosine kinase activity and the Ras signaling pathway. Proc Natl Acad Sci USA 91, 8602–8606PubMedCrossRefGoogle Scholar
  21. 21.
    Schottelius, A.J., Mayo, M.W., Sartor, R.B., and Baldwin, A.S. Jr. (1999) Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding J Biol Chem 274, 9558–9563CrossRefGoogle Scholar
  22. 22.
    Shames, B.D., Selzman, C.H., Meldrum, D.R., Pulido, E.J., Barton, H.A., Meng, X., Harken, A.H., and McIntyre, R.C Jr. (1998) Interleukin-10 stabilizes inhibitory IκB-α in human monocytes. Shock 10, 389–394PubMedCrossRefGoogle Scholar
  23. 23.
    Shanley, T.P., Vasi, N., and Denenberg, A. (2001) Regulation of chemokine expression by IL-10 in lung inflammation. Cytokine 12, 1054–1064CrossRefGoogle Scholar
  24. 24.
    Kasama, T., Strieter, R.M., Lukacs, N.W., Burdick, M.D., and Kunkel, S.L. (1994) Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol 152, 3559–3569PubMedGoogle Scholar
  25. 25.
    Kishore, R., Tebo, J.M., Kolosov, M., Hamilton, T.A. (1999) Clustered AU-rich elements are the target of IL-10-mediated mRNA destabilization in mouse macrophages. J Immunol 162, 2457–2461PubMedGoogle Scholar
  26. 26.
    Mulligan, M.S., Jones, M.L., Vaporciyan, A.A., Howard, M.C., and Ward, P.A. (1993) Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol 151, 5666–5674PubMedGoogle Scholar
  27. 27.
    Huaux, F., Louahed, J., Hudsmith, B., Meredith, C., Delos, M., Renauld, J.-C., and Lison, D. (1998) Role of interleukin-10 in the lung response to silica in mice. Am J Resp Cell Mol Biol 18, 51–59Google Scholar
  28. 28.
    Arai, T., Abe, K., Matsuoka, H., Yoshida, M., Mori, M., Goya, S., Kida, H., Nishino, K., Osaki, T., Tachibana, I., Kaneda, Y., and Hayashi, S. (2000) Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. Am J Physiol Lung Cell Mol Physiol 278, L914–L922PubMedGoogle Scholar
  29. 29.
    Morrison, D.F., Foss, D.L., and Murtaugh, M.P. (2000) Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia. Inf Immun 30, 4752–4758CrossRefGoogle Scholar
  30. 30.
    Gudmundsson, G., Bosch, A., Davidson, B.L., Berg, D.J., and Hunninghake, G.W. (1998) Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice. Am J Resp Cell Mol Biol 19, 812–818Google Scholar
  31. 31.
    Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K., and Muller, W. (1993) Interleukin-10 deficient mice develop chronic enterocolitis. Cell 75, 263–274PubMedCrossRefGoogle Scholar
  32. 32.
    Berg, D.J., Kuhn, R., Rajewsky, K., Muller, W., Menon, S., Davidson, N.J., Grunig, G., and Rennick, D. (1995) Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Schwartzman reaction but not of endotoxin tolerance. J Clin Invest 96, 2339–2347PubMedCrossRefGoogle Scholar
  33. 33.
    Shanley, T.P., Jones, M.L., Schmal, H., Friedl, H.P., and Ward, P.A. (1995) Regulatory effects of intrinsic interleukin-10 in IgG immune complex-induced lung injury. J Immunol 154, 3454–3460PubMedGoogle Scholar
  34. 34.
    Donnelly, S.C., Strieter, R.M., Reid, P.T., Kunkel, S.L., Burdick, M.D., Armstrong, I., Mackenzie, A., and Haslett, C. (1996) The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med 125, 191–196PubMedGoogle Scholar
  35. 35.
    Westendorp, R.G., Langermans, J.A., de Bel, C.E., Meinders, A.E., Vandenbroucke, J.P., van Furth, R., and van Dissel, J.T. (1995) Release of tumor necrosis factor: an innate host characteristic that may contribute to the outcome of meningococcal disease. J Infect Dis 171, 1057–1060PubMedCrossRefGoogle Scholar
  36. 36.
    Eskdale, J., and Gallagher, G. (1995) A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogen 42, 444–445Google Scholar
  37. 37.
    Eskdale, J., Gallagher, G., Verweij, C.L., Keijsers, V., Westendorp, R.G.J., and Huizinga, T.W.J. (1998) Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 95, 9465–9470PubMedCrossRefGoogle Scholar
  38. 38.
    Cherwinski, H.M., Schumacher, J.H., Brown, K.D., and Mosmann, T.R. (1987) Two types of mouse helper T cell clones III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays and monoclonal antibodies. J Exp Med 166, 1229–1244PubMedCrossRefGoogle Scholar
  39. 39.
    Smirnov, D.V., Smirnova, M.G., Korobko, V.G. and Frolova, E.I. (1995) Tandem arrangement of human genes for interleukin-4 and interleukin-13: resemblance in their organization. Gene 155, 277–281PubMedCrossRefGoogle Scholar
  40. 40.
    Zurawski, S.M., Vega, F., Huyghe, B., and Zurawski, G. (1993) Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J 12, 2663–2670PubMedGoogle Scholar
  41. 41.
    de Vries, J.E. (1996) Molecular and biological characteristics of interleukin-13. Chem Immunol 66, 101–111Google Scholar
  42. 42.
    Yanagawa, H., Sone, H., Haku, T., Mizuno, K., Yano, S., Ohmoto, Y., and Ogura, T. (1995) Contrasting effect of IL-13 on interleukin-1 receptor antagonist and proinflammatory cytokine production by human alveolar macrophages. Am J Respir Cell Mol Biol 12, 71–76PubMedGoogle Scholar
  43. 43.
    Berkman, N., John, M., Roesems, G., Jose, P.J., Barnes, P.J., and Chung, K.F. (1996) Interleukin-13 inhibits macrophage inflammatory protein-1α production from human alveolar macrophages and monocytes. Am J Respir Cell Mol Biol 15, 382–389PubMedGoogle Scholar
  44. 44.
    Mulligan, M.S., Warner, R.L., Foreback, J.L., Shanley, T.P., and Ward, P.A. (1997) Protective effects of IL-4, IL-10, IL-12 and IL-13 in IgG immune complex-induced lung injury: role of endogenous IL-12. J Immunol 159, 3483–3489PubMedGoogle Scholar
  45. 45.
    Watson, M.L., White, A.-M., Campbell, E.M., Smith, A.W., Uddin, J., Yoshimura, T., and Westwick, J. (1999) Anti-inflammatory actions of interleukin-13. Am J Respir Cell Mol Biol 20, 1007–1012PubMedGoogle Scholar
  46. 46.
    Baumhofer, J.M., Beinhauer, B.G., Wang, J.E., Brandmeier, H., Geissler, K., Losert, U., Phillip, R., Aversa, G., and Rogy, M.A. (1998) Gene transfer with IL-4 and IL-13 improves survival in lethal endotoxemia in the mouse and ameliorates peritoneal macrophages immune competence. Eur J Immunol 28, 610–615PubMedCrossRefGoogle Scholar
  47. 47.
    Muchamuel, T., Menon, S., Pisacane, P., Howard, M.C., and Cockayne, D.A. (1997) IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia: correlation with down-modulation of TNF-α, IFN-γ and IL-12 production. J Immunol 158, 2898–2903PubMedGoogle Scholar
  48. 48.
    Matsukawa, A., Hogaboam, C.M., Lukacs, N.W., Lincoln, P.M., Evanoff, H.L., Strieter, R.M., and Kunkel, S.L. (2000) Expression and contribution of endogenous IL-13 in an experimental model of sepsis. J Immunol 164, 2738–2744PubMedGoogle Scholar
  49. 49.
    Nelms, K., Keegan, A.D., Zamorano, J., Ryan, J.J., and Paul, W.E. (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17, 701–738PubMedCrossRefGoogle Scholar
  50. 50.
    Hilton, D.J., Zhang, J.-G., Metcalf, D., Alexander, W.S., Nicola, N.A., and Willson, T.A. (1996) Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sei USA 93, 497–501CrossRefGoogle Scholar
  51. 51.
    Misazaki, T., Kawahara, A., Fujii, H., Nakagawa, Y., Minami, Y., Liu, Z.-J., Oishi, I., Silvennoinen, O., Witthuhn, B.A., Ihle, J.N., and Taniguchi, T. (1994) Functional activation of Jakl and Jak3 by selective association with IL-2 receptor subunits. Science 266, 1045–1047CrossRefGoogle Scholar
  52. 52.
    Taketa, K., Tanaka, T., Shi, W., Matsumoto, M., Kashiwamura, S.-I., Nakanishi, K., Yoshida, N., Kishmoto, T., and Akira, S. (1996) Essential role of STAT6 on IL-4 signaling. Nature 380, 627–630CrossRefGoogle Scholar
  53. 53.
    Kaplan, M.H., Schindler, U., Smiley, S.T. and Grusby, M.J. (1996) STAT6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity 4, 313–319PubMedCrossRefGoogle Scholar
  54. 54.
    Takeda, K., Kamanaka, M., Tanaka, T., Kishimoto, T., and Akira, S. (1996) Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice. J Immunol 157, 3220–3232PubMedGoogle Scholar
  55. 55.
    Lentsch, A.B., Czermak, B.J., Jordan, J.A. and Ward, P.A. (1999) Regulation of acute lung inflammatory injury by endogenous IL-13. J Immunol 162, 1071–1076PubMedGoogle Scholar
  56. 56.
    Starr, R., Willson, T.A., Viney, E.M., Murray, L.J., Rayner, J.R., Jenkins, B.J., Gonda, T.J., Alexander, W.S., Metcalf, D., Nicola, N.A., and Hilton, D.J. (1997) A family of cytokine-inducible inhibitors of signaling. Nature 387, 917–921PubMedCrossRefGoogle Scholar
  57. 57.
    Jiang, H., Harris, M.B., and Rothman, P. (2000) IL-4/IL-13 signaling beyond JAK/STAT. J Allergy Clin Immunol 105, 1063–1070PubMedCrossRefGoogle Scholar
  58. 58.
    Wills-Karp, M. (1999) Immunologic basis of antigen-induced airway hyper-responsiveness. Ann Rev Immunol 17, 255–281CrossRefGoogle Scholar
  59. 59.
    Wills-Karp, M., Luyimbazi, J., Xu, X., Schofield, B., Neben, T.Y., Karp, C.L., and Donaldson, D.D. (1998) Interleukin-13: central mediator of allergic asthma. Science 282, 2258–2261PubMedCrossRefGoogle Scholar
  60. 60.
    Zhu, Z., Homer, R.J., Wang, Z., Chen, Q., Geba, G.P., Wang, J., Zhang, Y., and Elias, J.A. (1999) Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities and eotaxin production. J Clin Invest 103, 779–788PubMedCrossRefGoogle Scholar
  61. 61.
    Wierenga, E.A., and Messer, G. (2000) Regulation of interleukin-4 gene transcription: alterations in atopic disease? Am JRespir Crit Care Med 162, S81–S85Google Scholar
  62. 62.
    Heinzmann, A., Mao, X.Q., Akaiwa, M., Kreomer, R.T., Gao, P.S., Ohshima, K., Umeshita, R., Abe, Y., Braun, S., Yamashita, T., Roberts, M.H., Sugimoto, R., Arima, K., Arinobu, Y., Yu, B., Kruse, S., Enomoto, T., Dake, Y., Kawai, M., Shimazu, S., Sasaki, S., Adra, C.N., Kitaichi, M., Inoue, H., Yamauchi, K., Tomichi, N., Kurimoto, F., Hamasaki, N., Hopkin, J.M., Izuhara, K., Shirakawa, T., Deichmann, K.A. (2000) Genetic variants of IL-13 signaling and human asthma and atopy. Hum Mol Genet 9, 549–559PubMedCrossRefGoogle Scholar
  63. 63.
    McKenzie, A.N. (2000) Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13. Pharmacol Ther 88, 143–151PubMedCrossRefGoogle Scholar
  64. 64.
    Gadient, R.A., and Patterson, P.H. (1999) Leukemia inhibitory factor, interleukin-6, and other cytokines using the gpl30 transducing receptor: roles in inflammation and injury. Stem Cells 17, 127–137PubMedCrossRefGoogle Scholar
  65. 65.
    Kishimoto, T., Akira, S., and Taga, T. (1992) Interleukin-6 and its receptor: a paradigm for cytokines. Science 258, 593–597PubMedCrossRefGoogle Scholar
  66. 66.
    Chen-Kiang, S., Hsu, W., Natkunam, Y., and Zhang, X. (1993) Nuclear signaling by interleukin-6. Curr Opin Immunol 5, 124–128PubMedCrossRefGoogle Scholar
  67. 67.
    Donnelly, T.J., Meade, P., Jagels, M., Cryer, G., Lae, M.M., Hugli, T.E., Shoemaker, W.C., and Abraham, E. (1994) Cytokine, complement and endotoxin profiles associated with the adult respiratory distress syndrome after severe injury. Crit Care Med 22, 768–776PubMedCrossRefGoogle Scholar
  68. 68.
    Damas, P., Ledoux, D., Nys, M., DeGroote, D., Franchimont, P., and Lamy, M. (1991) Cytokine serum levels during severe sepsis in human: IL-6 as a marker of severity. Ann Surg 215, 356–366CrossRefGoogle Scholar
  69. 69.
    Roumen, T., Hendriks, J., van der Ven-Jongekrijg, G.A., Nieuwenhuijzen, R., Sauerwein, W., van der Meer, J.W.M. and Goris, R.J.A. (1993) Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Ann Surg 218, 769–776PubMedCrossRefGoogle Scholar
  70. 70.
    Aderka, D., Le, J., and Vilcek, J. (1989) IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol 143. 3517–3523PubMedGoogle Scholar
  71. 71.
    Shanley, T.P., Foreback, J.L., Remick, D.G., Ulich, T.R., Kunkel, S.L., and Ward, P.A. (1997) Regulatory effects of interleukin-6 in immunoglobulin G immune complex-induced lung injury. Am J Pathol 151, 193–203PubMedGoogle Scholar
  72. 72.
    Ulich, T.R., Yin, S., Guo, K., Yi, E.S., Remick, D.G., and del Castillo, J. (1991) Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor-ß inhibit acute inflammation. Am J Pathol 138, 1095–1101Google Scholar
  73. 73.
    Ulich, T.R., Guo, K., Remick, D.G., del Castillo, J. and Yin, S. (1990) Endotoxin-induced cytokine expression in vivo. III. IL-6 mRNA and serum expression and the in vivo hematologic effects of IL-6. J Immunol 146, 2316–2326Google Scholar
  74. 74.
    Denis, M. (1992) Interleukin-6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL-6 or direct administration of IL-6. J Leukocyte Biol 52, 197–201PubMedGoogle Scholar
  75. 75.
    Xing, Z., Gauldie, J., Cox, G., Baumann, H., Jordana, M., Lei, X.F., and Achong, M.K. (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101, 311–320PubMedCrossRefGoogle Scholar
  76. 76.
    Alcorn, J.M., Fierer, J., and Chojkier, M. (1992) The acute phase response protects mice from D-galactosamine sensitization to endotoxin and tumor necrosis factor-α. Hepatology 15, 122–129PubMedCrossRefGoogle Scholar
  77. 77.
    Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., and Kohler, G. (1994) Impaired immune and acute-phase responses in interleukin-6 deficient mice. Nature 368, 339–342PubMedCrossRefGoogle Scholar
  78. 78.
    Einarsson, O., Geba, G.P., Zhou, Z., Landry, M.L., Panettieri, R.A. Jr., Tristam, D., Welliver, R., Metinko, A., and Elias, J.A. (1993) Interleukin-11 in respiratory inflammation. Ann NY Acad Sci 89–101Google Scholar
  79. 79.
    Yin, T.G., and Yang, Y.-C. (1994) Involvement of MAP kinase and pp90rsk activation in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor and oncostatin M in mouse 3T3-L1 cells. J Biol Chem 269, 3731–3738PubMedGoogle Scholar
  80. 80.
    Teramura, M., Kobayashi, S., Hoshino, S., Oshimi, K., and Mizoguchi, H. (1992) Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood 79, 327–331PubMedGoogle Scholar
  81. 81.
    Tepler, I., Elias, L., Smith, J.W., Hussein, M., Rosen, G., Chang, A.Y., Moore, J.O., Gordon, M.S., Kuca, B., Beach, K.J., Loewy, J.W., Garnick, M.B., and Kaye, J.A. (1996) A randomized-placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 87, 3607–3614PubMedGoogle Scholar
  82. 82.
    Lentsch, A.B., Crouch, L.D., Jordan, J.A., Czermak, B.J., Yun, E.C., Guo, R., Sarma, V., Diehl, K.M., and Ward, P.A. (1999) Regulatory effects of interleukin-11 during acute lung inflammatory injury. J Leukoc Biol 66, 151–157PubMedGoogle Scholar
  83. 83.
    Sheridan, B.C., Dinarello, C.A., Meldrum, D.R., Fullerton, D.A., Selzman, C.H., and McIntyre, R.C. Jr. (1999) Interleukin-11 attenuates pulmonary inflammation and vasomotor dysfunction in endotoxin-induced lung injury. Am J Physiol 277, L861–L867PubMedGoogle Scholar
  84. 84.
    Waxman, A.B., Einarsson, O., Seres, T., Knickelbein, R.G., Warshaw, J.B., Johnston, R., Homer, R.J., and Elias, J.A. (1998) Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. J Clin Invest 101, 1970–1982PubMedCrossRefGoogle Scholar
  85. 85.
    Redlich, C.A., Gao, X., Rockwell, S., Kelly, M., and Elias, J.A. (1996) IL-11 enhances survival and decreases TNF production after radiation-induced thoracic injury. J Immunol 157, 1705–1710PubMedGoogle Scholar
  86. 86.
    Taga, T., and Kishimoto, T. (1997) Gpl30 and the interleukin-6 family of cytokines. Annu Rev Immunol 15, 797–819PubMedCrossRefGoogle Scholar
  87. 87.
    Yin, T., Yasukawa, K., Taga, T., Kishimoto, T., and Yang, Y.C. (1994) Identification of a 130 kilodalton tyrosine phosphorylated protein induced by interleukin-11, interleukin-6, leukemia inhibitory factor and oncostatin M as JAK2 kinase, which associates with gpl30 signal transducer. Exp Hematol 22, 467–472PubMedGoogle Scholar
  88. 88.
    Tsyganov, A. and Bolen, J. (1993) The Src family of tyrosine protein kinases in hematopoietic signal transduction. Stem Cells 11, 371–380CrossRefGoogle Scholar
  89. 89.
    Parker, P.J. and Waterfield, M.D. (1992) Phosphatidylinositol 3-kinase: a novel effector. Cell Growth Differ 3, 747–752PubMedGoogle Scholar
  90. 90.
    Pflanz, S., Kurth, I., Grotzinger, J., Heinrich, P.C., and Muller-Newen, G. (2000) Two different epitopes of the signal transducer gpl30 sequentially cooperate on IL-6-induced receptor activation. J Immunol 165, 7042–7049PubMedGoogle Scholar
  91. 91.
    Alexander, W.S., Starr, R., Metcalf, D., Nicholson, S.E., Farley, A., Elefanty, A.G., Brysha, M., Kile, B.T., Richardson, R., Baca, M., Zhang, J.G., Willson, T.A., Viney, E.M., Sprigg, N.S., Rakar, J., Mifsud, S., DiRago, L., Cary, D., Nicola, N.A., and Hilton, D.J. (1999) Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction. J Leukoc Biol 66, 588–92.PubMedGoogle Scholar
  92. 92.
    Endo, T.A., Masura, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., and Misawa, H. (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387, 921–924PubMedCrossRefGoogle Scholar
  93. 93.
    Diehl, S., Anguita, J., Hoffmeyer, A., Zapton, T., Ihle, J.N., Fikrig, E., and Rincon, M. (2000) Inhibition of Thl differentiation by IL-6 is mediated by SOCS1. Immunity 13, 805–815PubMedCrossRefGoogle Scholar
  94. 94.
    Trepicchio, W.L., Wang, L., Bozza, M., and Dorner, A.J. (1997) IL-11 regulates macrophage effector function through inhibition of nuclear factor-κB. J Immunol 159, 5661–5670PubMedGoogle Scholar
  95. 95.
    Elias, J.A., Zhu, Z., Chupp, G., and Homer, R.J. (1999) Airway remodeling in asthma. J Clin Invest 104, 1001–1006PubMedCrossRefGoogle Scholar
  96. 96.
    Wang, J., Homer, R.J., Chen, O., and Elias, J.A. (2000) Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation. J Immunol 165, 4051–4062PubMedGoogle Scholar
  97. 97.
    Wang, J., Homer, R.J., Hong, L., Cohn, L., Lee, C.G., Jung, S., and Elias, J.A. (2000) IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production. J Immunol 165, 2222–2231PubMedGoogle Scholar
  98. 98.
    Bone, R.C. (1996) Why sepsis trials failed. JAMA 276, 565–566PubMedCrossRefGoogle Scholar
  99. 99.
    Lemeshow, S., Teres, D., and Moseley, S. (1996) Statistical issues in clinical sepsis trials. In: Sepsis and multiple organ failure. Baltimore, MD: Williams and Wilkins. pp. 614–626Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Thomas P. Shanley
    • 1
  1. 1.Division of Critical Care MedicineChildren’s Hospital Medical Center and Children’s Hospital Research FoundationCincinnatiUSA

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