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

Objective-To evaluate the effect of aminoguanidine (AG) on de novo interleu kin 1 beta (IL1 beta), nitric oxide (NO), and interleukin I receptor antago nist (IL1ra) production by osteoarthritic human synovial tissue and articul ar cartilage cultures. Methods-Synovial tissue and cartilage, obtained during surgery from 29 pati ents undergoing total knee or hip replacement for osteoarthritis, were cut into small pieces and cultured in the presence or absence of lipopolysaccha ride (LPS) and test materials. IL1 beta, IL1ra, and NO were determined in c ulture 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 depen dent 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 mu g/ml) stimulated IL1 beta and NO release in the media in a dose dependent m anner (p<0.05 at 1 mmol/l and p<0.01 at 0.3 mmol/l, respectively). Hydrocor tisone (5 mug/ml) also significantly decreased LPS stimulated IL1 beta rele ase in media of synovial tissue and cartilage cultures and NO in media of s ynovial cultures. AG (0.3, 1, and 3 mmol/l) decreased LPS (1 mug/ml) stimul ated 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 10 0 <mu>g/ml). AG and nitroprusside at the concentrations used had no toxic e ffect on human synovial cells. Conclusions-NO synthase inhibitors may modulate osteoarthritis and articula r inflammatory processes not only by decreasing NO synthesis but also by th eir effects on IL beta and IL1ra production.