OBJECTIVE To evaluate the effect of aminoguanidine (AG) on de novo interleukin 1β (IL1β), nitric oxide (NO), and interleukin 1 receptor antagonist (IL1ra) production by osteoarthritic human synovial tissue and articular cartilage cultures.

RESULTS In synovial tissue cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 μg/ml) stimulated IL1β 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 μg/ml) stimulated IL1β 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 μg/ml) also significantly decreased LPS stimulated IL1β 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 μg/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 μg/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 μg/ml) stimulated IL1β release in media of synovial tissue cultures in a dose dependent manner (p<0.01 at 100 μg/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 ILβ and IL1ra production.