Dose dependent and additive effects of IL-1β and tumour necrosis factor (TNF)-α on IL-1 receptor antagonist (IL-1Ra) secretion in the presence of A77 1726 in human synovial fibroblasts. (a) Human osteoarthritis (OA) synovial fibroblasts (passage 4) were stimulated with various doses of IL-1β, or (b) various doses of TNF-α or with 0.25 ng/ml IL-1β and 1 ng/ml TNF-α together, in the absence (open symbols) or presence (closed symbols) of 100 μmol/l A77 1726, for 48 hours. A77 1726 was added 2 hours before stimulation with IL-1β. IL-1Ra concentrations in culture supernatants were measured using ELISA. Results are represented as means ± SEM of three determinations in a representative experiment. Similar results were obtained with cells from three different donors (three OA samples). *P < 0.05 versus control; &P < 0.05 versus cytokines without A77 1726.