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Cytokines

Opportunities for Therapeutic Intervention

  • Chapter
Drug Development

Abstract

The gastrointestinal (GI) tract is a major target organ for a number of infectious, inflammatory, neoplastic and functional diseases in humans. Cytokines (CKs) are involved in essentially all of these GI disorders, but they play a particularly dominant role in illnesses whose clinical symptoms are the result of immune-mediated, persistent inflammatory processes. Typical examples include chronic gastritis, celiac disease (gluten-sensitive enteropathy), Crohn’s disease (CD), and ulcerative colitis (UC). The pathogenesis of the last two entities, collectively named inflammatory bowel disease (IBD) because of common clinical and pathological manifestations, has been intensively investigated (Fiocchi, 1998), specifically regarding the role CKs play in mediating the chronic inflammation that damages the small or large bowel of affected individuals (Fiocchi, 1996). In addition, the explosion in the field of animal models of IBD that has occurred in the past decade has considerably expanded the involvement of CKs in intestinal inflammation. Therefore, IBD represents the ideal clinical and experimental model to describe CK abnormalities in the inflamed GI system, and to discuss the related opportunities for therapeutic intervention.

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References

  • Asseman C, Powrie F. Interleukin 10 is a growth factor for a population of regulatory T cells. Gut 1998; 42: 157–8.

    Article  PubMed  CAS  Google Scholar 

  • Babyatsky MW, Rossiter G, Podolsky DK. Expression of transforming growth factor a and 0 in colonic mucosa in inflammatory bowel disease. Gastroenterology 1996; 110: 975–984.

    Article  PubMed  CAS  Google Scholar 

  • Bank S, Sninsky C, Robinson M, Katz S, Singleton J, Miner P, et al. Safety and activity evaluation of rhIL-11 in subjects with active Crohn’s disease. Gastroenterology 1997; 112: A927.

    Google Scholar 

  • Barton BE. IL-6: insights into novel biological activities. Clin Immunol Immunopathol 1997; 5: 16–20.

    Article  Google Scholar 

  • Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 1996; 98: 1010–1020.

    Article  PubMed  CAS  Google Scholar 

  • Bertrand V, Quere S, Guimbaud R, Sogni P, Chauvelot-Moachon L, Tulliez M, et al. Effects of murine recombinant interleukin-10 on the inflammatory disease of rats transgenic for HLA-B27 and human beta 2 microglobulin. Eur Cytokine Netw 1998; 9: 161–170.

    PubMed  CAS  Google Scholar 

  • Braegger CP, Nicholls S, Murch SH, Stephens S, Macdonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339: 89–91.

    Article  PubMed  CAS  Google Scholar 

  • Cappello M, Keshav S, Prince C, Jewell DP, Gordon S. Detection of mRNA for macrophage products in inflammatory bowel disease by in situ hybridization. Gut 1992; 33: 1214–1219.

    Article  PubMed  CAS  Google Scholar 

  • Casini-Raggi V, Kam L, Chong YJT, Fiocchi C, Pizarro TT, Cominelli F. Mucosal imbalance of interleukin-1 and interleukin-1 receptor antagonist in inflammatory bowel disease: a novel mechanisms of chronic inflammation. J Immunol 1995; 154: 2434–2440.

    PubMed  CAS  Google Scholar 

  • Chantry D, Turner M, Abney E, Feldman M. Modulation of cytokine production by transforming growth factor-β1. J Immunol 1989; 142: 4295–4300.

    PubMed  CAS  Google Scholar 

  • Chomarat P, Bancherau J. Update on interleukin-4 and its receptor. Eur Cytokine Netw 1997; 8: 333–344.

    PubMed  CAS  Google Scholar 

  • Cominelli F, Bortolami M, Pizarro TT, Monsacchi L, Ferretti M, Brewer MT, Eisenberg SP, Ng RK. Rabbit interleukin-1 receptor antagonist. Cloning, expression, functional characterization, and regulation during intestinal inflammation. J Biol Chem 1994; 269: 6962–6971.

    PubMed  CAS  Google Scholar 

  • Cominelli F, Nast CC, Duchini A, Lee M. Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin1 in rabbit immune colitis. Gastroenterology 1992; 103: 65–71.

    PubMed  CAS  Google Scholar 

  • Costello R, Duffaud F. Pleiotropic effects of interleukin 7 and their pathologic and therapeutic implications. Eur J Med 1992; 2: 119–120.

    Google Scholar 

  • Davidson NJ, Hudak SA, Lesley RE, Menon S, Leach MW, Rennick DM. IL-12, but not IFN-gamma, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice. J Immunol 1998; 161: 3143–3149.

    PubMed  CAS  Google Scholar 

  • Demoulin JB, Renauld JC. Interleukin 9 and its receptor: an overview of structure and function. Inter Rev Immunol 1998; 16: 345–364.

    Article  CAS  Google Scholar 

  • De Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med 1995; 27: 537–541.

    Article  PubMed  Google Scholar 

  • De Vries JE, Zurawski G. Immunoregulatory properties of IL-13: Its potential role in atopic disease. Int Arch Allergy Immunol 1995; 106: 175–179.

    Article  PubMed  Google Scholar 

  • Dignass AU, Podolsky DK. Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor β. Gastroenterology 1993; 105: 1323–1332.

    Article  PubMed  CAS  Google Scholar 

  • Dinarello CA, Thompson RC. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 1991; 12: 404–410.

    Article  PubMed  CAS  Google Scholar 

  • Dinarello CA, Wolf SM. Role of interleukin-1 in disease. N Engl J Med 1993; 328: 106–113.

    Article  PubMed  CAS  Google Scholar 

  • Doe WF, Grimm MC. Colony-stimulating factors in inflammatory bowel disease, in Cytokines in Inflammatory Bowel Disease, Fiocchi C (ed.) R.G. Landes, Austin 1996,119–136.

    Google Scholar 

  • Du XX, Williams DA. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood 1994; 83: 2023–2030.

    PubMed  CAS  Google Scholar 

  • Eberhart CE, Dubois RN. Eicosanoids and the gastrointestinal tract. Gastroenterology 1995; 109: 285–301.

    Article  PubMed  CAS  Google Scholar 

  • Ehrhardt RO, Ludviksson BR, Gray B, Neurath M, Strober W. Induction and prevention of colonic inflammation in IL-2-deficient mice. J Immunol 1997; 158: 566–73.

    PubMed  CAS  Google Scholar 

  • Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology 1995; 109: 1344–67.

    Article  PubMed  CAS  Google Scholar 

  • Finch PW, Pricolo V, Wu A, Finkelstein SD. Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease. Gastroenterology 1996; 110: 441–451.

    Article  PubMed  CAS  Google Scholar 

  • Fiocchi C. Cytokines in Inflammatory Bowel Disease . R.G. Landes, Austin 1996.

    Google Scholar 

  • Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115: 182–205.

    Article  PubMed  CAS  Google Scholar 

  • Fuss IJ, Neurath M, Boirivant M, Klein JS, Delamotte C, Strong SA, Fiocchi C, Strober W. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’ s disease LP manifest increased secretion of IFN-y, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 1996; 157: 1261–1270.

    PubMed  CAS  Google Scholar 

  • Grimm MC, Doe WF. Chemokines in inflammatory bowel disease mucosa: expression of RANTES, macrophage inflammatory protein (MIP)-1a, MIP11β, and y-interferon-inducible protein 10 by macrophages, lymphocytes, endothelial cells, and granulomas. Inflamm Bowel Dis 1996; 2: 88–96.

    PubMed  CAS  Google Scholar 

  • Groux H, O’ Garra A, Bigler M, Rouleau M, Antonenko S, De Vries JE, Roncarolo MG. CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737–742.

    Article  PubMed  CAS  Google Scholar 

  • Hogaboam CM, Vallance BA, Kumar A, Addison CL, Graham FL, Gauldie J, Collins SM. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest 1997; 100: 2766–2776.

    Article  PubMed  CAS  Google Scholar 

  • Isaacs KL, Sartor RB, Haskill S. Cytokine messenger RNA profiles in inflam matory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 1992; 103: 1587–1595.

    PubMed  CAS  Google Scholar 

  • Ito H, Fathman CG. CD45RBhigh CD4+ T cells from IFN-gamma knockout mice do not induce wasting disease. J Autoimmun 1997; 10: 455–459.

    Article  PubMed  CAS  Google Scholar 

  • Izzo RS, Witkon K, Chen AI, Hadjiyane C, Weinstein MI, Pellecchia C. Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. Am J Gastroenterol 1992; 87: 1447–1452.

    PubMed  CAS  Google Scholar 

  • Izzo RS, Witkon K, Chen AI, Hadjiyane C, Weinstein MI, Pellecchia C. Neutrophil-activating peptide (interleukin-8) in colonic mucosa from patients with Crohn’s disease. Scand J Gastroenterol 1993; 28: 296–300.

    Article  PubMed  CAS  Google Scholar 

  • Keates S, Keates AC, Mizoguchi E, Bhan A, Kelly CP. Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis. Am J Phvsiol 1997; 273: G75—G82.

    Google Scholar 

  • Kelsall BL, Stuber E, Neurath M, Strober W. Interleukin-12 production by dendritic cells. The role of CD4O—CD4OL interactions in Th1 T-cell responses. Ann NY Acad Sci 1996; 795: 116–126.

    Article  PubMed  CAS  Google Scholar 

  • Kohno K, Kurimoto M. Interleukin 18, a cytokine which resembles IL-1 structurally and IL-12 functionally but exerts its effects independently of both. Clin Immunol Immunopathol 1998; 86: 11–15.

    Article  PubMed  CAS  Google Scholar 

  • Koike M, Takatsu K. IL-5 and its receptor: which role do they play in the immune response. Int Arch Allergy Immunol 1994; 104: 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Kucharzik T, Stoll R, Lugering N, Domschke W. Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD). Clin Exp Immunol 1995; 100: 452–456.

    Article  PubMed  CAS  Google Scholar 

  • Kugathasan S, Willis J, Dahms BB, O’Riordan MA, Hupertz V, Binion DG, Boyle JT, Fiocchi C. Intrinsic hyperreactivity of mucosal T-cells to interleukin-2 in pediatric Crohn’s disease. J Pediatr 1998;133: 675–681.

    Article  PubMed  CAS  Google Scholar 

  • Kusugami K, Fukatsu A, Tanimoto M, Shinoda M, Haruta J-I, Kuroiwa A, et al. Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent. Dig Dis Sci 1995; 40: 949–959.

    Article  PubMed  CAS  Google Scholar 

  • Kusugami K, Youngman KR, West GA, Fiocchi C. Intestinal immune reactivity to interleukin 2 differs among Crohn’s disease, ulcerative colitis and control. Gastroenterology 1989: 97: 1–9.

    PubMed  CAS  Google Scholar 

  • Ludviksson BR, Ehrhardt RO, Strober W. TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice. J Immunol 1997a: 159: 3622–3628.

    PubMed  CAS  Google Scholar 

  • Ludviksson BR, Gray B, Strober W, Ehrhardt RO. Dysregulated intrathymic development in the IL-2-deficient mouse leads to colitis-inducing thymocytes. J Immunol 1997b; 158: 104–111.

    PubMed  CAS  Google Scholar 

  • Luster AD. Chemokines: Chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436–445.

    Article  PubMed  CAS  Google Scholar 

  • Macdermott RP, Sanderson IR, Reinecker H-C. Central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis 1998; 4: 54–67.

    Article  PubMed  CAS  Google Scholar 

  • Mahida YR, Wu K, Jewell DP. Enhanced production of interleukin 1-β3 by mononuclear cells isolated from mucosa with active ulcerative colitis and Crohn’s disease. Gut 1989; 30: 835–838.

    Article  PubMed  CAS  Google Scholar 

  • Matsuura T, Kusugami K, Morise K, Fiocchi C. Interleukin-2 and interleukin2 receptor in inflammatory bowel disease, in Cytokines in Inflammatory Bowel Disease Fiocchi C (ed.) R.G. Landes, Austin, 1996, pp. 41–55.

    Google Scholar 

  • Mcinnes IB, Liew FY. Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis. Immunol Today 1998; 19: 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F. Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 1997; 112: 1169–1178.

    Article  PubMed  CAS  Google Scholar 

  • Mosmann TR, Sad S. Expanding universe of T-cell subsets: Thl, Th2 and more. Immunol Today 1996; 17: 138–146.

    Article  PubMed  CAS  Google Scholar 

  • Mullin GE, Maycon ZR, Braun-Elwert L, Cerchia R, James SP, Katz S, et al. Inflammatory bowel disease mucosal biopsies have specialized lymphokine mRNA profiles. Inflamm Bowel Dis 1996; 2: 16–26.

    PubMed  CAS  Google Scholar 

  • Neurath MF, Fuss I, Kelsall B, Meyer Zum Buschenfelde KH, Strober W. Effect of IL-12 and antibodies to IL-12 on established granulomatous colitis in mice. Ann NY Acad Sci 1996b; 795: 368–370.

    Article  PubMed  CAS  Google Scholar 

  • Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W. Experimental granulomatous colitis in mice is abrogated by induction of TGFbeta-mediated oral tolerance. J Exp Med 1996a; 183: 2605–2616.

    Article  PubMed  CAS  Google Scholar 

  • Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995; 182: 1281–1290.

    Article  PubMed  CAS  Google Scholar 

  • Pallone F, Fais S, Boirivant M. Interferon system in inflammatory bowel disease, in Cytokines in Inflammatory Bowel Disease Fiocchi C (ed.) R.G. Landes, Austin, 1996, pp. 57–67.

    Google Scholar 

  • Podolsky DK. Lessons from genetic models of inflammatory bowel disease. Acta Gastroenterol Belg 1997; 60: 163–165.

    PubMed  CAS  Google Scholar 

  • Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL. Critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J Exp Med 1996; 183: 2669–2674.

    Article  PubMed  CAS  Google Scholar 

  • Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL. Inhibition of Thl responses prevents inflammatory bowel disease in SCID mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1994; 1: 553–562.

    Article  PubMed  CAS  Google Scholar 

  • Qiu BS, Pfeiffer CJ, Keith JC, Jr. Protection by recombinant human interleukin 11 against experimental TNB-induced colitis in rats. Dig Dis Sci 1996; 41: 1625–1630.

    Article  PubMed  CAS  Google Scholar 

  • Reinecker H-C, Loh EY, Ringler DJ, Metha A, Rombeau JL, Macdermott RP. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology 1995; 108: 40–50.

    Article  PubMed  CAS  Google Scholar 

  • Reinecker H-C, Steffen M, Witthoeft T, Pflueger I, Schreiber S, Macdermott RP, Raedler A. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’ s disease. Clin Exp Immunol 1993; 94: 174–181.

    Article  PubMed  CAS  Google Scholar 

  • Rennick DM, Fort MM, Davidson NJ. Studies with IL-10-/- mice: an overview. J Leukoc Biol 1997; 61: 389–396.

    PubMed  CAS  Google Scholar 

  • Rink L, Kirchner H. Recent progress in the tumor necrosis-a field. Int Arch Allergy Immunol 1996; 111: 199–209.

    Article  PubMed  CAS  Google Scholar 

  • Sakai T, Kusugami K, Nishimura H, Ando T, Yamaguchi T, Ohsuga M, et al. Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease. Gastroenterology 1998; 114: 1237–1243.

    Article  PubMed  CAS  Google Scholar 

  • Sartor RB. How relevant to human inflammatory bowel disease are current animal models of intestinal inflammation? Aliment Pharmacol Ther 1997; 11 (Suppl 3): 89–96; discussion 96–97.

    Article  PubMed  Google Scholar 

  • Simpson SJ, Shah S, Comiskey M, De Jong YP, Wang B, Mizoguchi E, Bhan AK, Terhorst C. T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J Exp Med 1998; 187: 1225–1234.

    Article  PubMed  CAS  Google Scholar 

  • Sonoda E, Matsumoto R, Hitoshi Y, Ishii T, Sugimoto M, Araki S, et al. Transforming growth factor β induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med 1989; 170: 1415–1420.

    Article  PubMed  CAS  Google Scholar 

  • Sparano JA, Brandt LJ, Dutcher JP, Dubois JS, Atkins MB. Symptomatic exacerbation of Crohn disease after treatment with high-dose interleukin2. Ann Intern Med 1993; 118: 617,618.

    Google Scholar 

  • Spencer D, Levine A. Local production of IL-12 by lamina propria mononuclear cells is triggered with the onset of colitis and subsides during chronic disease. Gastroenterology 1998; 114: A-1089.

    Article  Google Scholar 

  • Stack WA, Mann SD, Roy AJ, Heath P, Sopwith M, Freeman J, et al. Randomised controlled trial of CDP571 antibody to tumour necrosis factor-a in Crohn’s disease. Lancet 1997; 349: 521–524.

    Article  PubMed  CAS  Google Scholar 

  • Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, et al. Tumor necrosis factor-a, interleukin-1β3, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci 1992; 37: 818–826.

    Article  PubMed  CAS  Google Scholar 

  • Targan SR, Hanauer SB, Vandeventer SJH, Mayer L, Present DH, Braakman T, et al. Short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor a for Crohn’ s disease. N Engl J Med 1997; 337: 1029–1035.

    Article  PubMed  CAS  Google Scholar 

  • Theze J, Alzari PM, Bertoglio J. Interleukin 2 and its receptors: recent advances and new immunological functions. Immunol Today 1996; 17: 481–486.

    Article  PubMed  CAS  Google Scholar 

  • Tomoyose M, Mitsuyama K, Ishida H, Toyonaga A, Tanikawa K. Role of interleukin-10 in a murine model of dextran sulfate sodium-induced colitis. Scand J Immunol 1998; 33: 435–440.

    CAS  Google Scholar 

  • Trinchieri G, Scott P. Role of interleukin 12 in the immune response, disease, and therapy. Immunol Today 1994; 15: 460–463.

    Article  PubMed  CAS  Google Scholar 

  • Vandeventer SJH, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Gastroenterology 1997; 113: 383–389.

    Article  CAS  Google Scholar 

  • Watanabe M, Ueno Y, Yajima T, Okamoto S, Hayashi T, Yamazaki M, et al. Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med 1998; 187: 389–402.

    Article  PubMed  CAS  Google Scholar 

  • Weiner HL. Oral tolerance: immune mechanisms and tratment of autoimmune diseases. Immunol Today 1997; 18: 335–343.

    Article  PubMed  CAS  Google Scholar 

  • West GA, Matsuura T, Levine AD, Klein JS, Fiocchi C. Interleukin-4 in inflammatory bowel disease and mucosal immune reactivity. Gastroenterol02V 1996: 110: 1683–1695.

    Article  CAS  Google Scholar 

  • Wright NA, Poulsom R, Stamp G, Vannoorden S, Sarraf C, Elia G, et al. Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. Gastroenterology 1993; 194: 12–20.

    Google Scholar 

  • yYoung HA, Hardy KJ. Role of interferon-yin immune cell regulation. Immunol Today 1995; 58: 373–381.

    Google Scholar 

  • Youngman KR, Simon PL, West GA, Cominelli F, Rachmilewitz D, Klein JS, Fiocchi C. Localization of intestinal interleukin 1 activity, protein and gene expression to lamina propria cells. Gastroenterology 1993; 104: 749–758.

    PubMed  CAS  Google Scholar 

  • Z’Graggen K, Walz A, Mazzucchelli L, Strieter RM, Mueller C. C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease. Gastroenterology 1997; 113: 808–816.

    Article  PubMed  Google Scholar 

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Authors
  1. Alan D. Levine
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  2. Claudio Fiocchi
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Editors and Affiliations

  1. School of Pharmacy, University of Wisconsin, Madison, WI, USA

    Timothy S. Gaginella

  2. Parke-Davis Pharmaceutical Research Division, Ann Arbor, MI, USA

    Antonio Guglietta

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Levine, A.D., Fiocchi, C. (2000). Cytokines. In: Gaginella, T.S., Guglietta, A. (eds) Drug Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-202-9_3

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  • DOI: https://doi.org/10.1007/978-1-59259-202-9_3

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