Interleukin 16 expression in relation to disease activity in rheumatoid arthritis

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease of u nknown etiology characterized by an infiltration of CD4+ T lymphocytes with in the rheumatoid synovium. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. We analyzed the expression of a T cell deri ved cytokine, Interleukin 16 (IL-16), in relation to disease activity to ch aracterize its biologic function in RA. Methods. Secreted IL-16 was measured by enzyme immunoassay in sera and syno vial fluids (SF) from 25 patients with RA in comparison to 20 control sampl es from patients with osteoarthritis (OA). IL-16 expression in peripheral b lood mononuclear cells (PBMC) was characterized by now cytometric analysis after intracellular cytokine staining for IL-16. rn synovial tissue specime ns, IL-16 mRNA expression was analyzed by real-time quantitative reverse tr anscriptase polymerase chain reaction (RT-PCR). In parallel, expression of IL-16 was localized in synovial tissues by in situ hybridization and immuno histochemistry. Results were analyzed in relation to disease activity. Results. IL-16 was detected at significantly higher levels in sera and SF o f patients with RA in comparison to OA (p < 0.001). Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ T cells constitutively expressed the IL-16 protein. Ln synovial tissues, IL-16 mRNA levels were s ignificantly elevated in comparison to OA controls (p < 0.001). In situ hyb ridization for IL-16 producing cells revealed a predominant accumulation of IL-16 positive cells within the inflammatory infiltrates. A significant co rrelation between IL-16 expression and local inflammatory activity could no r be established (r = 0.27, p = 0.19) by microscopic analysis of the synovi al cell infiltrate. In addition, no significant association was observed be tween serum, SE and synovial tissue expression of IL-16 and clinical diseas e activity in RA. Conclusion. These data suggest IL-16 might play a role in the pathogenesis of chronic inflammation in lih. The lack of significant correlation between IL-16 expression, clinical disease activity, and local inflammatory activi ty suggests a regulatory rather than a proinflammatory function for IL-16 i n the pathogenesis of chronic synovial inflammation in RA.