role of interleukin 16 in the immunopathogenesis of rheumatoid arthritis

ABSTRACT

Rheumatoid Arthritis [RA] is a chronic inflammatory disease characterized by hyperplasia of the synovium and excessive cellular infiltration, which leads to progressive joint destruction. We analyzed, interleukin 16 [IL16], in relation to disease activity to characterize its biologic function in RA. Secreted IL-16 was measured by enzyme immunoassay in sera from 30 RA patients and 30 healthy controls [HC], and also in synovial fluid [SF] from 16 RA patients and 15 patients with non-RA synovitis as controls. IL-16 expression in peripheral blood mononuclear cells [PBMC] was characterized by flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, both were done Immunohistochemistry for localization of IL-16, and histopathology, in which the tissue scored semiquantitatively for synovial hyperplasia and cellular infiltration. IL-16 was detected at significantly higher levels in sera and SF of RA patients in comparison to HC and non-RA synovitis [p<0.001 and p<0.0001 respectively]. Also, IL-16 was detected significantly higher in SF in comparison to sera in RA patients [p<0.001]. Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ cells expressed IL-16 protein. Also, immunohistochemistry revealed more CD4+ and less frequency of CD8+ cells in synovial infiltration. A significant correlation between IL-16 expression and local inflammatory activity could not be established [p>0.21] by microscopic analysis of the synovial cells infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL-16 and clinical disease activity in RA [p>0.61, p>0.5 and p>0.42 respectively]. This indicated that, IL-16 played a regulatory rather than a proin-flammatory role in the immunopathogenesis of RA