The Effect of Sulfasalazine on Rheumatoid Arthritic Synovial Tissue Chemokine Production

Abstract

Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which chemokines are thought to recruit leukocytes and induce angiogenesis. The aim of this study was to investigate the effects of sulfasalazine (SASP) and its metabolites, sulfapyridine (SP), and 5-aminosalicylic acid (5ASA) on chemokine production by RA synovial tissue explants and interleukin (IL)-1β-stimulated RA synovial tissue fibroblasts using enzyme-linked immunosorbent assays and flow cytometry. Synovial tissue explants from RA patients secreted a decreased amount of the chemokines IL-8 and growth-related gene product α (GROα) when treated with SASP over a broad range of concentrations based on the typical clinical dosage of 2 g/day. SP had a significant effect in that it decreased RA synovial tissue explant secretion of IL-8 (22%), GROα (55%), and monocyte chemotactic protein-1 (MCP-1) (42%) ( P < 0.05). 5ASA had no effect on RA synovial tissue explant production of IL-8 and MCP-1, while increasing GROα production. In IL-1β-stimulated RA synovial tissue fibroblasts, SASP significantly increased chemokine secretion, while SP significantly decreased IL-8 (24%) and GROα (21%) secretion ( P < 0.05). Flow cytometry showed that the number of IL-8 expressing RA synovial tissue fibroblasts did not significantly change following SP treatment. These data suggest that SASP may function to reduce inflammation in RA through the effects of its metabolite SP to reduce the secretion of the inflammatory chemokines IL-8, GROα, and MCP-1.