THE SYNOVIAL EXPRESSION AND SERUM LEVELS OF INTERLEUKIN-6, INTERLEUKIN-11, LEUKEMIA INHIBITORY FACTOR, AND ONCOSTATIN-M IN RHEUMATOID-ARTHRITIS

Objective, To determine the expression of interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their ma jor cellular sources in the joints of rheumatoid arthritis (RA) patien ts, as well as the correlation of circulating levels of these IL-6-typ e cytokines and C-reactive protein (CRP). Methods. Messenger RNA (mRNA ) and protein levels for IL-6, IL-11, LIF, and OSM were determined by using reverse transcription-polymerase chain reaction and enzyme-linke d immunosorbent assay, respectively. Results. Cells isolated from the synovium of RA patients expressed mRNA for IL-6, IL-11, LIF, and OSM a t higher levels than did synovial cells from osteoarthritis (OA) patie nts, and spontaneously released greater quantities of these proteins i n culture, Fibroblast cell lines derived from Ri synovium were able to produce IL-6, IL-11, and LIF, but not OSM, when stimulated with IL-1 and tumor necrosis factor alpha. OSM was found to be produced spontane ously by synovial tissue macrophages. IL-6, IL-11, LIF, and OSM were p resent in synovial fluid from the RA patients; levels of IL-6, LIF, an d OSM were present in significantly greater quantities in RA patients than in OA patients, However, only IL-6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, whil e other IL-6-type cytokines were not detected. Conclusions. IL-6, IL-1 1, LIF, and OSM are all produced in large amounts at the site of disea se activity, but IL-6 derived from synovial fibroblasts may be the maj or hormone-like mediator that induces the hepatic synthesis of acute-p hase proteins in RA.