THU0031 High synovial fluid and serum il-18 levels in patients with rheumatoid and psoriatic arthritis

Abstract

Background Studies suggest that interleukin-1 (IL-1) is the key mediator of arthritis and we have investigated the effect of IL-1 on cartilage degradation. We demonstrated that IL-1 inhibited proteoglycan (PG) synthesis via enhanced nitric oxide (NO) synthesis by chondrocytes. We also demonstrated that IL-1 increased intracellular Ca 2+ ion concentration ([Ca 2+ ]i) of chondrocytes. On the other hand, interleukin-4 (IL-4) is a T-cell derived 20 kDa glycoprotein and antagonise the cytokine mediated cartilage degradation.Objectives We examined the effect of IL-4 on IL-1-enhanced NO synthesis in parallel with intracellular Ca levels and PG synthesis. Methods Bovine articular chondrocytes were obtained. PG synthesis was measured with [35S] sulfate incorporation. NO levels were measured by use of an NO chemiluminescence analyzer. Ca 2+ imaging was carried out with Fura2-AM loaded chondrocyte using the digital fluorescence-imaging system. Results In the presence of IL-4, IL-1-enhanced NO release was completely abolished. IL-4 functions mainly as anti-inflammatory, as well as IL-10 and IL-13. To our knowledge, this is the first report demonstrating an inhibitory effect of IL-4 in NO release stimulated by IL-1. Alterations in [Ca 2+ ]i provide a ubiquitous cell signalling system that mediates a variety of cellular process. IL-1 evoked an increase in the levels of [Ca 2+ ]i, a response characterised by a steep onset and followed by a slower decline to preexisting values. IL-4 also abolished the IL-1induced [Ca 2+ ]i increase in the chondrocytes. We examined the effect of IL-4 on PG synthesis. Although IL-4 did not affect PG synthesis, IL-1-inhibited PG synthesis was reversed with the addition of IL-4. It is possible that IL-4 reversed the IL-1-inhibited PG synthesis through the inhibition of NO synthesis and [Ca 2+ ]i increase. Conclusion IL-4 plays a chondroprotecting effect antagonising with IL-1-inhibited PG synthesis.