A77 1726 increases IL-1 receptor antagonist (IL-1Ra) secretion in human synovial fibroblasts and articular chondrocytes in the presence of IL-1β. (a) Human osteoarthritis (OA) synovial fibroblasts (passage 2) and (b) de-differentiated human OA articular chondrocytes (passage 7) were stimulated (closed symbols) or not (open symbols) with 1 ng/ml IL-1β alone or in combination with 50 μmol/l or 100 μmol/l A77 1726 for 48 hours. (c) Freshly isolated normal human articular chondrocytes were stimulated (black columns) or not (white columns) with 100 μmol/l A77 1726 alone or in combination with 1 ng/ml IL-1β 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 expressed as means ± SEM for three determinations in a representative experiment. Similar results were obtained with cells from three different donors (three OA samples) for synovial fibroblasts and three different donors (three OA samples) for de-differentiated chondrocytes. On freshly isolated chondrocytes, a stimulatory effect of A77 1726 was observed in cells from 12 (five normal adult, six OA and one normal paediatric sample) out of 18 different donors. *P < 0.05 versus control; &P < 0.05 versus IL-1β alone.