• cytokines
• interleukin 18
• inflammation
• rheumatoid arthritis

• CIA, collagen induced arthritis
• IFN, interferon
• IL, interleukin
• RA, rheumatoid arthritis
• RT-PCR, reverse transcriptase-polymerase chain reaction
• TNF, tumour necrosis factor

Mediators produced by innate immune response cells such as macrophages can profoundly influence adaptive immunity. Recent studies have shown that interleukin (IL) 18 has an influential role in inflammatory response. Recent data are presented illustrating the importance of IL18 in the induction and perpetuation of chronic inflammation during experimental and clinical rheumatoid synovitis. These findings suggest that antagonists to IL18 may have a role in the treatment of organ specific autoimmune diseases.

There is currently considerable interest in the interactive role of innate and adaptive immunity. A large number of mediators have been implicated, particularly those derived from the innate response that can drive the adaptive immunity. In this short review, we will summarise the work carried out in our laboratory on the roles of interleukin (IL) 18 in adaptive immune response and in perpetuating chronic organ specific inflammatory reactions. We will focus primarily on rheumatoid arthritis (RA). The processes that initiate and perpetuate RA are currently unclear. Successful clinical targeting of tumour necrosis factor (TNF) α therefore represents an exciting and important advance, not only in therapeutics but also in understanding the disease pathogenesis. However, non-responder or partial responder patients are not uncommon, and inflammatory disease usually flares on discontinuation of treatment.^1,2 This carries significant pathogenetic implications for existing disease models. Moreover, it exemplifies the clinical necessity for generation of further novel, pathogenesis led interventions. One approach to the detection of novel synovial inflammatory pathways is to establish events that regulate synovial TNFα production. Recently, our group has explored the expression of novel cytokine activities in RA synovial membrane that could perpetuate inflammatory synovitis, in particular through modulation of T lymphocyte function and TNFα expression by IL18, an innate cytokine produced principally by macrophages after activation by a range of stimuli, including infection and stress.