Interleukin-18, a proinflammatory cytokine

Although IL-18 is an inducer of IFN-gamma and Th1 responses, IL-18 is a pro inflammatory cytokine by several criteria. In several animal models, antibo dies that neutralize endogenous IL-18 reduce the severity of disease. Endot oxin lethality is prevented by anti-IL-18. Even in models that are interfer on-gamma independent, neutralization of IL-18 prolongs survival. Anti-IL-18 also protects the liver against cellular injury induced by toxins or activ ated T cells. In models of hepatic melanoma metastasis, IL-18 blockade redu ces the adherence of malignant cells by preventing IL-18 upregulation of va scular endothelial adhesion-1 molecule expression. IL-18 and IL-12 act syne rgistically to stimulate T cells and natural killer cells to produce IFN-ga mma but neutralization of IL-18 prevents IL-12 induction of IFN-gamma. IL-1 8, like several cytokines, can be used to enhance host defense against tumo rs in mice a mechanism that is most often IFN-gamma -dependent. Nevertheles s, it is the proinflammatory portfolio of IL-18 which likely contributes to enhanced host defenses. In models or arthritis, lung injury or inflammator y bowel disease, neutralization of IL-18 reveals the important role of this cytokine in mediating inflammation.