In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs

Abstract

Since non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for inhibition of inflammation, an in vivo assay for leukotaxis would be of use in comparing the biological activity effects of the agents. Here, the effects of 4 different NSAIDs on in vivo leukocyte accumulation was determined by quantitating N-formyl-methionyl-leucylphenylalanine induced leukotaxis in the rabbit anterior eye chamber. New Zealand white female rabbits were treated for three days with the following regimens: ibuprofen or aspirin, 0.1, 1.0, 10.0 or 100.0 mg/kg/day, indomethacin or flurbiprofen, 0.01, 0.1, 1.0, or 10.0 mg/kg/day. Indomethacin and flurbiprofen significantly reduced leukotaxis in a dose of 10.0 mg/kg/day. Aspirin was associated with a weak inhibition of leukotaxis. Ibuprofen had biphasic effects, 1.0 mg/kg/day potentiated and 10 mg/kg/day inhibited leukotaxis, whereas leukocyte accumulation was uneffected by a high dose (100.0 mg/kg/day). These results suggest that modulation of leukotaxis by NSAIDs may reflect a differential dose-response sensitivity of lipoxygenase and cycloxygenase pathways.

The dorsal skinfold chamber: A valuable model for the in vivo evaluation of topical formulations

“…They are primarily mediated by inhibition of cyclooxygenase (COX)‐1 and COX‐2 activity . So far, the inhibitory effects of topical diclofenac formulations on leucocyte recruitment during inflammation have been described in several in vivo models, such as the corneal inflammation model in rabbits and the periodontal inflammation model in rats . In line with these previous analyses, we herein found that diclofenac‐containing gel effectively suppresses leucocyte adhesion and transmigration into inflamed tissue.…”