Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis

Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI 1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-alpha (mean 1.3 +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/- 0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro alpha plays an important role in the ingress of PMNs into the RA joint.