IL-18 Is Produced by Articular Chondrocytes and Induces Proinflammatory and Catabolic Responses

• Published in: The Journal of immunology (1950) Vol. 162; no. 2; pp. 1096 - 1100
• Main Authors: Olee, Tsaiwei, Hashimoto, Sanshiro, Quach, Jacqueline, Lotz, Martin
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.1999
• Subjects: Arthritis - immunology; Arthritis - metabolism; Arthritis - pathology; Cartilage, Articular - immunology; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cell Division - drug effects; Cell Division - immunology; Chondrocytes - drug effects; Chondrocytes - immunology; Chondrocytes - metabolism; Chondrocytes - pathology; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Growth Inhibitors - pharmacology; Growth Inhibitors - physiology; Humans; Interleukin-18 - biosynthesis; Interleukin-18 - genetics; Interleukin-18 - physiology; Knee Joint; Nitric Oxide - biosynthesis; Protein Biosynthesis; Proteoglycans - metabolism; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; Transforming Growth Factor beta - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.2.1096

IL-18, a cytokine originally identified as IFN-gamma-inducing factor, is a member of the IL-1 family of proteins. Because IL-1alpha and IL-1beta are important mediators in the pathogenesis of arthritis, the present study addresses the expression of IL-18 and its role in regulating in articular chondrocytes. IL-18 mRNA was induced by IL-1beta in chondrocytes. Chondrocytes 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 production. IL-18 stimulated the expression of several genes in normal human articular chondrocytes including inducible nitric oxide synthase, inducible cyclooxygenase, IL-6, and stromelysin. Gene expression was associated with the synthesis of the corresponding proteins. Treatment of normal human articular cartilage with IL-18 increased the release of glycosaminoglycans. These finding identify IL-18 as a cytokine that regulates chondrocyte responses and contributes to cartilage degradation.