EnhancedProduction ofMonocyte Chemoattractant Protein-1 inRheumatoid Arthritis

Cells within thesynovial tissue mayrecruit mononuclear phagocytes into thesynovial fluid andtissues ofarthritic patients. We investigated theproduction ofthechemotactic cytokine monocyte chemoattractant protein-i (MCP-1) using sera, synovial fluid, synovial tissue, aswell asmacrophages andfibroblasts isolated fromsynovial tissues from80arthritic patients. MCP1levels weresignificantly higher (P<0.05) insynovial fluid fromRApatients (mean25.5±8.1 ng/mlISEI) compared to synovial fluid fromosteoarthritis (OA)patients (0.92±0.08), orfrompatients withother arthritides (2.9±1.5). MCP-1levelsinRA sera(8.44±2.33) weresignificantly greater than MCP-1innormal sera (0.16±0.06). Thequantities ofRAsynovial fluid IL-8, which ischemotactic forneutrophils andlymphocytes, andMCP-1werestrongly positively correlated (P <0.05). Toexamine thecellular source ofMCP-1, RAsynovial tissue macrophages andfibroblasts wereisolated. Synovial tissue fibroblasts didnotexpress MCP-1mRNA,butcould be induced toproduce MCP-1bystimulation witheither IL-1#, tumornecrosis factor-alpha (TNF-a), orLPS.Incontrast, unlikenormal peripheral blood monocytes oralveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1mRNA andantigen. Immunohistochemical analysis ofsynovial tissue showed that asignificantly greater percentage ofRAmacrophages (50±8%) ascompared toeither OA macrophages (5±2)ornormalmacrophages (1±0.3) reacted withanti-MCP-1 antibodies. Inaddition, thesynovial lining layer reacted with MCP-1inbothRAandOA synovial tissues. Incontrast, onlyaminority ofsynovial fibroblasts (18±8%) fromRAsynovium werepositive forimmunolocalization ofMCP-1.These results suggest that synovial production ofMCP-1mayplayanimportant role intherecruitment of mononuclear phagocytes during inflammation associated with RA andthatsynovial tissue macrophages arethedominant source ofthis cytokine. (J.Clin. Invest. 1992. 90:772-779.)