Differential effects of inhibition of isoforms of cyclooxygenase (COX-1, COX-2) in chronic inflammation

摘要: Objective and Design: The anti-inflammatory effects of therapeutic dosing drugs with greater selectivity for the inhibition constitutive (COX-1) or inducible isoform (COX-2) cyclooxygenase were assessed in a model chronic inflammation.¶Methods: murine granulomatous tissue air pouch involves subcutaneous injection into dorsum mice followed 24 h later by intrapouch an inflammatory stimulus (0.5 ml Freund's complete adjuvant containing 0.1% croton oil). Aspirin, more selective vitro COX-1 (10,200 mg/kg) nimesulide, inhibitor COX-2 (0.5, 5 mg/kg) dosed p.o. daily from 3 days after stimulus. Granuloma dry weight, vascularity COX activity (measured as PGE2) at various time points throughout lesion to resolution day 28. A second inhibitor, NS 398 (0.1, 1, 10 mg/kg), was its on granuloma measured 7 days.¶Results: Aspirin (200 mg/kg) significantly inhibited levels PGE2 course lower dose (10 mg/kg) 14. Nimesulide (5 mg/kg) however, increased 5 21, but 0.5 mg/kg without effect. reduced weight 14 had no effect 7. In contrast, nimesulide NS-398 all doses stimulus.¶Conclusion: this inflammation, aspirin, is effective than inhibitors inhibiting activity.