Interleukin-18 as a potential target in inflammatory arthritis

To date, the mechanisms underlying the aetiology of rheumatoid arthritis (RA) remain poorly understood. However, targeting tumour necrosis factor (TNF)-α in the clinic represents an exciting and important advance, in both therapeutics and understanding of disease pathogenesis. Non-responder or partial responder patients are not uncommon and disease usually flares on discontinuation of treatment [1]. Thus novel, pathogenesis-led interventions are required. Our group has studied cytokine networks in RA synovial membrane, identifying pathways regulating T lymphocyte function and TNF-α production that result in inflammatory synovitis. Interleukin (IL)-18, a member of the interleukin-1 cytokine superfamily, recognized as an important regulator of both innate and acquired immunity, is one such cytokine. We identified IL-18 expression within the inflamed synovium of RA patients [2] and similar reports document its presence in other autoimmune and chronic inflammatory diseases, in cancers and in numerous infectious diseases. This editorial will review function and focus on recent data including an article in this issue of Clinical and Experimental Immunology in which Ye and colleagues [3] provide data supporting a role for IL-18 in the induction and perpetuation of chronic inflammation during experimental and clinical RA. Activities in additional disease states and during infection have been discussed recently elsewhere [4–6].