BALANCE OF IL-1 RECEPTOR ANTAGONIST IL-1-BETA IN RHEUMATOID SYNOVIUM AND ITS REGULATION BY IL-4 AND IL-LO/

The spontaneous production of IL-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) by rheumatoid arthritis (RA) synovium, and the reg ulation of their production by IL-4 and IL-10, were studied. Supernata nts from cultured synovium pieces from 19 RA patients were assayed for IL-1 beta and IL-1Ra production using ELISA and RIA, respectively. Af ter 10 days of culture, spontaneous production of IL-1Ra was 1.42 +/- 0.43 ng/ml/100 mg of synovium whereas spontaneous production of IL-1 b eta was 4.03 +/- 0.90 ng/ml/100 mg of synovium (n = 19). The addition of IL-4 reduced IL-1 beta production by 2.3-fold (p = 0.001) and incre ased that of IL-1Ra by 2.8-fold (p = 0.003). IL-10 had no significant effect on IL-1Ra production and suppressed IL-1 beta production (prima rily in samples producing high levels of IL-1 beta). However, IL-10 wa s less potent than IL-4 in suppressing IL-1 beta production. IL-1Ra wa s mainly produced by rheumatoid synovial monocytes/macrophages. IL-4 w as more potent than IL-10 in inducing IL-1Ra production by monocytes/m acrophages purified from RA synovium, as well as from RA blood. Thus, RA synovium is characterized by an imbalance between IL-1Ra and IL-1 b eta production, in favor of the latter. IL-4, and to a lesser extent I L-10, shift this balance in favor of an anti-inflammatory situation.