Macrophage inflammatory protein-1α: A novel chemotactic cytokine for macrophages in rheumatoid arthritis

Abstract

We have shown that human macrophages (mφs) play an important role in the elaboration of chemotactic cytokines in rheumatoid arthritis (RA) (Koch, A. E., S. L. Kunkel, J. C. Burrows, H. L. Evanoff, G. K. Haines, R. M. Pope, and R. M. Strieter. 1991. J. Immunol. 147:2187; Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, and R. M. Strieter. 1992. J. Clin. Invest. 90:772; Koch, A. E., P. J. Polverini, S. L. Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M. Strieter. 1992. Science ( Wash. DC). 258:1798). Recently, mφ inflammatory protein-1 (MIP-1α), a cytokine with chemotactic activity for mφs and neutrophils (PMNs), has been described. We have examined the production of MIP-1α using sera, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic patients. MIP-1α was higher in RA SF (mean, 29±8 ng/ml [SE]) compared with other forms of arthritis (2.8±1.7), or osteoarthritis (0.7±0.4; P < 0.05). RA SF MIP-1α was greater than that found in either RA or normal peripheral blood (PB) (P < 0.05). Anti-MIP-1α neutralized 36±3% (mean±SE) of the chemotactic activity for mφs, but not PMNs, found in RA SFs. RA SF and PB mononuclear cells produced antigenic MIP-1α. Mononuclear cell MIP-1α production was augmented with phytohemagglutinin or LPS. Isolated RA ST fibroblast production of antigenic MIP-1α was augmented upon incubation of cells with LPS, and to a lesser extent with tumor necrosis factor-α. Isolated RA ST mφs expressed constitutive MIP-1α mRNA and antigenic MIP-1α. Using ST immunohistochemistry, MIP-1α+ cells from RA compared with normal were predominantly mφs and lining cells (P < 0.05). These results suggest that MIP-1α plays a role in the selective recruitment of mφs in synovial inflammation associated with RA.