Inhibitor of interleukin-2 synthesis and response in rheumatoid synovial fluid.
We studied the effects of a factor present in rheumatoid arthritis (RA) synovial fluid (SF) on interleukin-2 (IL-2)-dependent cell proliferation and on the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells. RA SF suppressed the responsiveness of a mouse T cell line (HT-2) to IL-2, indicating that it contained an inhibitor of the IL-2 response. When RA SF was fractionated by Sephadex G-200 gel filtration, the inhibitory activity was detected mainly in fractions with a molecular weight of approximately 150,000, but was also found in a 15-19-kd fraction. Removal of IgG from the 150-kd fraction, by means of an anti-IgG affinity column, did not reduce the activity of the fraction, nor was activity found in the eluted IgG. The inhibitory fractions reduced mouse thymocyte proliferative responses to IL-1 in the presence of phytohemagglutinin, and reduced the production of IL-2 by human peripheral blood mononuclear cells, but did not inhibit IL-1-induced human foreskin fibroblast proliferation; this suggests that the factor was not an IL-1 inhibitor. The inhibitory activity of the RA SF factor was blocked by an antibody against an inhibitor of IL-2 that was purified from a culture of the human monocytic leukemia cell line, THP-1. This finding also supports the conclusion that RA SF contains an IL-2 inhibitory factor. The observed inhibition of both IL-2 synthesis and IL-2 response suggests that the target of the inhibition was the T lymphocyte.
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002850:Chromatography, Gel; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D013582:Synovial Fluid / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
D007074:Immunoglobulin G; D007375:Interleukin-1; D007376:Interleukin-2; D008222:Lymphokines; C046147:interleukin 2 inhibitor