Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition

• Published in: The Journal of immunology (1950) Vol. 141; no. 8; pp. 2612 - 2618
• Main Authors: Symons, JA, Wood, NC, Di Giovine, FS, Duff, GW
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.10.1988; American Association of Immunologists
• Subjects: Adult; Antigen-Antibody Reactions; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - metabolism; Biological and medical sciences; Chromatography, Gel; Diseases of the osteoarticular system; Humans; Inflammatory joint diseases; Interleukin-1 - antagonists & inhibitors; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - metabolism; Leukocytes, Mononuclear - analysis; Medical sciences; Middle Aged; Receptors, Interleukin-2 - immunology; Receptors, Interleukin-2 - isolation & purification; Receptors, Interleukin-2 - metabolism; Solubility; Synovial Fluid - analysis; Human; Immunopathology; Diseases of the osteoarticular system; Monokine; Immune regulation; Lymphokine; Inflammatory joint disease; Soluble form; Enzyme immunoassay; Synovial fluid; Chronic; Membrane receptor; Interleukin 2; Radioimmunoassay; Rheumatoid arthritis; Interleukin 1; Serum; ELISA assay
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.141.8.2612

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.