The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis

Objective. To evaluate the: effects of treatment with interleukin-1 recepto r antagonist (IL-1Ra) on synovial tissue in rheumatoid arthritis (RA). Methods. Twelve patients with RA entering a randomized clinical trial of hu man recombinant IL-1Ra underwent synovial biopsies before and after treatme nt. Cellular infiltration and adhesion molecule expression were evaluated a fter immunohistochemical staining. Results. There was a notable reduction in intimal layer macrophages and sub intimal macrophages and lymphocytes after treatment with IL-1Ra at 150 mg/d ay (n = 3. Increased cellular infiltration was observed in all patients rec eiving placebo (n = 3); variable changes were observed after IL-1Ra 30 mg/d ay (n = 6). In a limited study of adhesion molecule expression, down-regula tion of E-selectin and vascular cell adhesion molecule-1 was observed after treatment with IL-1Ra 150 mg:day, but not after IL-1Ra 30 mg/day or placeb o. The apparent arrest of progressive joint damage seen in four patients af ter treatment with IL-1Ra was associated with reduced intimal layer macroph age accumulation in all patients. Conclusion. Treatment of RA with IL-1Ra resulted in reduced mononuclear cel l infiltration of synovial membrane, which may represent the in vivo inhibi tion of biologically relevant IL-1 beta -mediated pathogenic effects.