Novel pro-inflammatory interleukins: potential therapeutic targets in rheumatoid arthritis

Among potential targets for nonspecific anti-inflammatory immunointervention, three pro-inflammatory interleukins (ILs) have recently been found to play a pivotal role in rheumatoid arthritis (RA). IL-15 has both chemoattractant and proinflammatory properties and may promote bone destruction. IL-17, a product of T lymphocytes, has proinflammatory effects and induces production of metalloproteinases such as MMP-1. IL-18 not only has proinflammatory, angiogenic, and chemoattractant effects but also promotes cartilage destruction. These cytokines are potential targets for specific or nonspecific anti-inflammatory therapy. Thus, blocking IL-15 by its receptor reduces the severity of experimental collagen-induced arthritis (CIA). In this model, IL-17 levels fall after administration of anti-inflammatory cytokines such as IL-4 or IL-13. Finally, monoclonal anti-IL-18 antibodies prevent streptococcal cell wall arthritis, and IL-18 binding protein, which is a naturally occurring IL-18 inhibitor, prevents CIA.