Down regulation of interleukin 1β production in human osteoarthritic synovial tissue and cartilage cultures by aminoguanidine

Objective-To evaluate the effect of aminoguanidine (AG) on de novo interleukin 1 beta (IL1 beta), nitric oxide (NO), and interleukin I receptor antagonist (IL1ra) production by osteoarthritic human synovial tissue and articular cartilage cultures. Methods-Synovial tissue and cartilage, obtained during surgery from 29 patients undergoing total knee or hip replacement for osteoarthritis, were cut into small pieces and cultured in the presence or absence of lipopolysaccharide (LPS) and test materials. IL1 beta, IL1ra, and NO were determined in culture media. The inducible nitric oxide synthase inhibitor, AG, was added to cultures in various concentrations (0.3-3 mmol/l). Results-In synovial tissue cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 mug/ml) stimulated IL1 beta and NO release in the media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.05 at 0.3 mmol/l, respectively). In articular cartilage cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 mug/ml) stimulated IL1 beta and NO release in the media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.01 at 0.3 mmol/l, respectively). Hydrocortisone (5 mug/ml) also significantly decreased LPS stimulated IL1 beta release in media of synovial tissue and cartilage cultures and NO in media of synovial cultures. AG (0.3, 1, and 3 mmol/l) decreased LPS (1 mug/ml) stimulated IL1ra levels in media of synovial tissue cultures in a dose dependent manner (p<0.05 at 1 mmol/l) but increased LPS (1 <mu>g/ml) stimulated IL1ra release in media of cartilage cultures (p<0.01 at 3 mmol/l). The NO donor, nitroprusside (10, 30, 100, and 300 pg/ml) stimulated IL1<beta> release in media of synovial tissue cultures in a dose dependent manner (p<0.01 at 100 <mu>g/ml). AG and nitroprusside at the concentrations used had no toxic effect on human synovial cells. Conclusions-NO synthase inhibitors may modulate osteoarthritis and articular inflammatory processes not only by decreasing NO synthesis but also by their effects on IL beta and IL1ra production.