Antiinflammatory effects of etoricoxib alone and combined with NSAIDs in LPS-induced reactive arthritis

Nonsteroidal anti-inflammatory drugs constitute the primary therapeutic approach in reactive arthritis. Here, we compared etoricoxib, a specific COX-2 inhibitor, with other cyclooxygenase inhibitors on articular incapacitation, edema, leukocyte migration, and gastric damage, in a model of LPS-induced reactive arthritis in rats. E. coli Lipopolysaccharide was injected into a carrageenan-primed knee-joint of rats. The effects of etoricoxib, piroxicam, indomethacin, as well the combination of etoricoxib either with piroxicam or indomethacin, were evaluated on articular incapacitation and edema. Afterwards, the synovial leukocyte ontent and the stomach bleeding points were counted. Etoricoxib, piroxicam, and indomethacin dose-dependently inhibited incapacitation and edema. However, only etoricoxib inhibited both mononuclear and polymorphonuclear leukocyte migration. Piroxicam inhibited only mononuclear migration, while indomethacin even increased polymorphonuclear content in inflamed synovia. Associating etoricoxib with either subeffective doses of piroxicam or indomethacin did not enhance the hyponociceptive or the antiedematogenic effect, but prevented the anti-leukocyte migration effect and increased gastric damage. The present results suggest that the selective COX-2 inhibitor etoricoxib could be a better option than non-selective COX inhibitors, since it presented a potent inhibitory effect on the clinical signals and also a potent inhibition on cell migration.