A proinflammatory role for IL-18 in rheumatoid arthritis

Gracie, J. A. et al. (1999) A proinflammatory role for IL-18 in rheumatoid arthritis. Journal of Clinical Investigation, 104(10), pp. 1393-1401. (doi:10.1172/JCI7317) (PMID:10562301) (PMCID:PMC409841)

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Abstract

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-γ production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-α synthesis by CD14+ macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-α and IFN-γ synthesis was suppressed by IL-10 and TGF-β. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-α and IL-1β, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund’s adjuvant–immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Professor Foo and Xu, Dr Damo and Foulis, Dr Alan and Field, Dr Max and Gracie, Dr J A and Leung, Dr Bernard and Gilmour, Miss Ashley
Authors: Gracie, J. A., Forsey, R. J., Chan, W. L., Gilmour, A., Leung, B. P., Greer, M. R., Kennedy, K., Carter, R., Wei, X.-Q., Xu, D., Field, M., Foulis, A., Liew, F. Y., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Investigation
Publisher:Americal Society for Clinical Investigation
ISSN:0021-9738
ISSN (Online):1558-823

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