Modulation of leukotaxis by ibuprofen. A quantitative determination in vivo

Abstract

The purpose of this study was to evaluate the rabbit anterior eye chamber as a quantitative measure of leukotaxis using 51Cr-labeled homologous leukocytes and then to determine the effects of ibuprofen on N-formyl-methionyl-leucyl-phenylalanine (FMLP) -induced leukotaxis. Leukocyte accumulation was assessed at various intervals (0-24 h) after instillation of FMLP (10(-4) M, 40 microliters) and at various doses (FMLP 10(-6)-10(-4) M). New Zealand white rabbits (2.6-3.0 kg) were treated with ibuprofen for three days with the following regimens: 8.0, 17.5, 35.0, 70.0 mg/kg/ day. Leukocyte quantitation was determined using a direct cell count and recovery of 51Cr-labeled leukocytes from anterior eye chamber aspirations 3 h after their injection into the systemic circulation. FMLP induced a dose-dependent accumulation of leukocytes. Leukocyte influx into the anterior eye chamber increased between 2 and 4 h after FMLP instillation, peaking between 4 and 6 h, then resolving after 8 h. Ibuprofen inhibited leukocyte accumulation into the anterior eye chamber in a dose dependent fashion with a maximum (90.0 +/- 1.4%, X +/- SEM) inhibition with 70 mg/kg/day and an ID50 of 8 mg/kg/day. In conclusion, the anterior eye chamber FMLP-stimulated leukotaxis assay is useful to evaluate the role of pharmacologic agents. Here, ibuprofen was found to inhibit leukotaxis in a dose-dependent manner.