Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition.
An ELISA was used to measure soluble IL-2R (sIL-2R) in the sera and synovial fluids of patients with rheumatic diseases. Patients with rheumatoid arthritis had raised levels of sIL-2R both in their sera and in their synovial fluid compared to patients with osteoarthritis and age-matched healthy controls. Mononuclear cells from the synovial fluid of rheumatoid arthritis patients were found to produce spontaneously high levels of sIL-2R which eluted at approximately m.w. 40,000 on gel filtration. In contrast, autologous peripheral blood cells only produced comparable levels upon stimulation with mitogenic lectin. Sequential studies indicated that serum sIL-2R levels were highly correlated with disease activity, indicating that measurement of sIL-2R may be a useful clinical marker in the future. Within the joint, synovial fluid sIL-2R levels correlated significantly with immunoreactive IL-1 beta levels, providing evidence for a role of IL-1 in immune activation in the synovium. In synovial fluids, sIL-2R level also correlated with functional inhibition of IL-2-driven responses in vitro. Furthermore, sIL-2R immunoreactivity in synovial fluid eluted at m.w. 100,000 coeluting with IL-2-inhibitory activity and consistent with a role for sIL-2R in down-regulation of IL-2 responses. The abnormal m.w. may be accounted for by complex formation in the synovial fluid. Given the ability of sIL-2R to bind IL-2, the presence of sIL-2R within the joint may contribute to the well documented "IL-2 defect" seen in rheumatoid arthritis.
Symons
J A
JA
University of Edinburgh, Department of Medicine, U.K.
Wood
N C
NC
Di Giovine
F S
FS
Duff
G W
GW
D000328:Adult; D000937:Antigen-Antibody Reactions; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D002850:Chromatography, Gel; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000032:analysis; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012995:Solubility; D013582:Synovial Fluid / Q000032:analysis
D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2