IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses

IL-18, a cytokine originally identified as IFN-gamma-inducing factor, is a member of the IL-1 family of proteins, Because IL-1 alpha and IL-1 beta are important mediators in the pathogenesis of arthritis, the present study ad dresses the expression of IL-18 and its role in regulating in articular cho ndrocytes, IL-18 mRNA was induced by IL-1 beta in chondrocytes, Chondrocyte s produced the IL-18 precursor and in response to IL-1 stimulation secreted the mature form of IL-18, Studies on IL-18 effects on chondrocytes showed that it inhibits TGF-beta-induced proliferation and enhances nitric oxide p roduction. IL-18 stimulated the expression of several genes in normal human articular chondrocytes including inducible nitric oxide synthase, inducibl e cyclooxygenase, IL-6, and stromelysin, Gene expression was associated wit h the synthesis of the corresponding proteins. Treatment of normal human ar ticular cartilage with IL-18 increased the release of glycosaminoglycans. T hese finding: identify IL-18 as a cytokine that regulates chondrocyte respo nses and contributes to cartilage degradation.