620
Views
5
CrossRef citations to date
0
Altmetric
REVIEW ARTICLE

Th17-cytokine blockers as a new approach for treating inflammatory bowel disease

, &
Pages 172-178 | Received 01 Jul 2010, Accepted 21 Sep 2010, Published online: 30 Nov 2010

References

  • Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.
  • Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573–621.
  • Fais S, Capobianchi MR, Pallone F, Di Marco P, Boirivant M, Dianzani F, . Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers. Gut. 1991;32:403–7.
  • Isaacs KL, Sartor RB, Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology. 1992;103:1587–95.
  • Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, . Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997;112:1169–78.
  • Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, . Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157: 1261–70.
  • Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, . A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997;337:1029–35.
  • Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, . Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007; 132:52–65.
  • Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, . A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology. 2005;129:807–18.
  • Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369:1641–57.
  • Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease. Am J Gastroenterol. 2008;103:944–8.
  • Ma HL, Napierata L, Stedman N, Benoit S, Collins M, Nickerson-Nutter C, . Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum. 62:430–40.
  • Quispel R, van der Worp HB, Pruissen M, Schipper ME, Oldenburg B. Fatal aseptic meningoencephalitis following infliximab treatment for inflammatory bowel disease. Gut. 2006;55:1056.
  • Nunez Martinez O, Ripoll Noiseux C, Carneros Martin JA, Gonzalez Lara V, Gregorio Maranon HG. Reactivation tuberculosis in a patient with anti-TNF-alpha treatment. Am J Gastroenterol. 2001;96:1665–6.
  • Schneeweiss S, Korzenik J, Solomon DH, Canning C, Lee J, Bressler B. Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther. 2009;30:253–64.
  • Passarini B, Infusino SD, Barbieri E, Varotti E, Gionchetti P, Rizzello F, . Cutaneous manifestations in inflammatory bowel diseases: eight cases of psoriasis induced by anti-tumor-necrosis-factor antibody therapy. Dermatology. 2007;215:295–300.
  • Neurath MF, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, . The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J Exp Med. 2002;195:1129–43.
  • Parrello T, Monteleone G, Cucchiara S, Monteleone I, Sebkova L, Doldo P, . Up-regulation of the IL-12 receptor beta 2 chain in Crohn's disease. J Immunol. 2000; 165:7234–9.
  • Reinisch W, de Villiers W, Bene L, Simon L, Racz I, Katz S, . Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm Bowel Dis. 2010; 16:233–42.
  • Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, . Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut. 2006;55:1131–7.
  • Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.
  • Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, . Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis. 2008;14:437–45.
  • Dambacher J, Beigel F, Zitzmann K, De Toni EN, Göke B, Diepolder HM, . The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut. 2009;58:1207–17.
  • Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, . IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 2006;290:G827–38.
  • Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, . Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–61.
  • Monteleone G, Monteleone I, Fina D, Vavassori P, Del Vecchio Blanco G, Caruso R, . Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology. 2005;128: 687–94.
  • Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, . Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 2007;448:480–3.
  • Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, . IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.
  • Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, . IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484–7.
  • Sarra M, Monteleone I, Stolfi C, Fantini MC, Sileri P, Sica G, . Interferon-gamma-expressing cells are a major source of interleukin-21 in inflammatory bowel diseases. Inflamm Bowel Dis. 2010;16:1332–9.
  • Caruso R, Fina D, Peluso I, Stolfi C, Fantini MC, Gioia V, . A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Gastroenterology. 2007;132:166–75.
  • Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC. Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002;51:818–26.
  • Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, . Evidence for a cross-talk between human neutrophils and Th17 cells. Blood. 2010;115:335–43.
  • Monteleone G, Caruso R, Fina D, Peluso I, Gioia V, Stolfi C, . Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21. Gut. 2006;55:1774–80.
  • Liu Z, Yang L, Cui Y, Wang X, Guo C, Huang Z, . Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:1133–44.
  • Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls JK. Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis. 2006;12:382–8.
  • Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003;14:155–74.
  • Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, . Regulation of inflammatory responses by IL-17F. J Exp Med. 2008;205:1063–75.
  • Ito R, Kita M, Shin-Ya M, Kishida T, Urano A, Takada R, . Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. Biochem Biophys Res Commun. 2008;377:12–16.
  • Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB, . Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology. 2007;132:2359–70.
  • Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, . IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–40.
  • Brombacher F, Kastelein RA, Alber G. Novel IL-12 family members shed light on the orchestration of Th1 responses. Trends Immunol. 2003;24:207–12.
  • Tajima M, Wakita D, Noguchi D, Chamoto K, Yue Z, Fugo K, . IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells. J Exp Med. 2008;205:1019–27.
  • Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, . A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15:1016–22.
  • O'Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, . A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol. 2009;10:603–9.
  • Leppkes M, Becker C, Ivanov II, Hirth S, Wirtz S, Neufert C, . RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology. 2009;136:257–67.
  • Noguchi D, Wakita D, Tajima M, Ashino S, Iwakura Y, Zhang Y, . Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a T(h)17-independent manner. Int Immunol. 2007;19:1431–40.
  • McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, . TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8:1390–7.
  • Fina D, Sarra M, Fantini MC, Rizzo A, Caruso R, Caprioli F, . Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology. 2008;134: 1038–48.
  • Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, . IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–6.
  • Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, . Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006;203: 2473–83.
  • Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, . IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med. 2006;203:2485–94.
  • Izcue A, Hue S, Buonocore S, Arancibia-Carcamo CV, Ahern PP, Iwakura Y, . Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity. 2008;28:559–70.
  • Becker C, Dornhoff H, Neufert C, Fantini MC, Wirtz S, Huebner S, . Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol. 2006;177:2760–4.
  • Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, . Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest. 2008;118:2269–80.
  • Kamada N, Hisamatsu T, Honda H, Kobayashi T, Chinen H, Takayama T, . TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease. Inflamm Bowel Dis. 2010;16:568–75.
  • Mannon PJ, Fuss IJ, Mayer L, Elson CO, Sandborn WJ, Present D, . Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med. 2004;351:2069–79.
  • Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, . A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology. 2008;135:1130–41.
  • Fuss IJ, Becker C, Yang Z, Groden C, Hornung RL, Heller F, . Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm Bowel Dis. 2006;12:9–15.
  • Burakoff R, Barish CF, Riff D, Pruitt R, Chey WY, Farraye FA, . A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. Inflamm Bowel Dis. 2006;12: 558–65.
  • Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, . Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 184:5298–307.
  • Nowell MA, Williams AS, Carty SA, Scheller J, Hayes AJ, Jones GW, . Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol. 2009;182:613–22.
  • Murase A, Okumura T, Sakakibara A, Tonai-Kachi H, Nakao K, Takada J. Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation. Eur J Pharmacol. 2008;580:116–21.
  • Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, . IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest. 2008;118:534–44.
  • Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, . Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet. 2007;39:830–2.
  • Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, . 16.A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.
  • Festen EA, Goyette P, Scott R, Annese V, Zhernakova A, Lian J, . Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut. 2009;58: 799–804.
  • Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, . Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis. 2008;14:204–12.
  • Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, . IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Inves. 2009;119:2052–61.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.