Effect of indomethacin on IL-1 receptor antagonist (IL-1Ra) secretion in human synovial fibroblasts and articular chondrocytes. (a) Human osteoarthritis (OA) synovial fibroblasts (passage 1), (b) de-differentiated human OA articular chondrocytes (passage 2), and (c) freshly isolated human OA articular chondrocytes were stimulated or not (control; white bars) with 1 ng/ml IL-1β (hatched bars), the combination of IL-1β and 5 μg/ml indomethacin (gray bars), or the combination of IL-1β and 100 μmol/l A77 1726 (black bars) for 48 hours. Indomethacin or A77 1726 was added 2 hours before stimulation with IL-1β. IL-1Ra concentrations in culture supernatants were measured by ELISA. Results are presented as means ± SEM of three determinations in a representative experiment. Similar results were obtained with cells from six different donors (six OA samples) for synovial fibroblasts, seven different donors (seven OA samples) for de-differentiated chondrocytes and six different donors (three normal and three OA samples) for freshly isolated chondrocytes. *P < 0.05 versus control; &P < 0.05 versus IL-1β alone; **P < 0.001 versus IL-1β alone.