Anti-interleukin-18 therapy in murine models of inflammatory bowel disease.
Interleukin (IL)-18 is a cytokine with a broad array of effector functions, the most prominent of which is to act synergistically with IL-12 in interferon-gamma production and the induction of a strong T-helper-1-mediated immune response. In addition, IL-18 also upregulates the production of proinflammatory cytokines such as IL-1 and tumor necrosis factor-alpha. Analysis of IL-18-deficient mice revealed an important role of IL-18 in the activation of macrophages and natural killer cells in the context of infection with intracellular bacteria or parasites. In humans, it was reported that IL-18 is elevated at sites of inflammation in inflammatory bowel disease (IBD), particularly in Crohn's disease, suggesting a possible role for IL-18 in the development and persistence of IBD. In this review we summarize recent findings on the functional role of IL-18 in the pathogenesis of colitis with a special focus on murine models of IBD. The neutralizing mouse anti-mouse IL-18 antibodies generated in our group should facilitate the evaluation of the efficiency of therapeutic blockade of endogenous IL-18 in chronic mouse models of colitis besides the use of recombinant forms of the inhibitory IL-18-binding protein.
Lochner
Matthias
M
Institute for Medical Microbiology, Immunology and Hygiene and Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
Förster
Irmgard
I
D000818:Animals; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D020382:Interleukin-18 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016372:RNA, Antisense / Q000627:therapeutic use
D019138:Antibodies, Blocking; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D016372:RNA, Antisense