Interleukin-18, a proinflammatory cytokine.
Although IL-18 is an inducer of IFN-gamma and Th1 responses. IL-18 is a proinflammatory cytokine by several criteria. In several animal models. antibodies that neutralize endogenous IL-18 reduce the severity of disease. Endotoxin lethality is prevented by anti-IL-18. Even in models that are interferon-y independent, neutralization of IL-18 prolongs survival. Anti-IL-18 also protects the liver against cellular injury induced by toxins or activated T cells. In models of hepatic melanoma metastasis. IL-18 blockade reduces the adherence of malignant cells by preventing IL-18 upregulation of vascular endothelial adhesion-1 molecule expression. IL-18 and IL-12 act synergistically to stimulate I cells and natural killer cells to produce IFN-gamma but neutralization of IL-18 prevents IL-12 induction of IFN-gamma. IL-18. like several cytokines. can be used to enhance host defense against tumors in mice a mechanism that is most often IFN-gamma-dependent. Nevertheless. it is the proinflammatory portfolio of IL-18 which likely contributes to enhanced host defenses. In models or arthritis, lung injury or inflammatory bowel disease, neutralization of IL-18 reveals the important role of this cytokine in mediating inflammation.
Dinarello
C A
CA
University of Colorado Health Sciences Center, Denver 80262, USA.
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000906:Antibodies; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020382:Interleukin-18; C118370:interleukin-18 binding protein