EXPRESSION OF MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR IN RHEUMATOID-ARTHRITIS - REGULATION OF ITS PRODUCTION IN SYNOVIAL-CELLS BY INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR

Objective. To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). Methods. MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse-transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. Results. High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast-like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin-1 (IL-1) and tumor necrosis factor in vitro. IL-1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. Conclusion. Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.