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Anti-interleukin-18 therapy in murine models of inflammatory bowel disease
Matthias Lochner1, Irmgard Förster
1Institute for Medical Microbiology, Immunology and Hygiene and Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
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.
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.