THE INHIBITORY EFFECT OF IBUDILAST ON LATE BRONCHIAL RESPONSE (LBR) IN OA SENSITIZED GUINEA PIGS

Abstract

To investigate whether Ibudilast (3-isobutyryl-2-isopropyl pyrazolo [1, 5-a] pyridine), which is reported to be antagonistic to leukotriene (LT) C₄, D₄ and PAF, inhibits late bronchial response (LBR) in ovalbumin (OA) sensitized guinea pigs or not, the following studies were carried out. Twenty guinea pigs were actively sensitized by inhalation of OA at days 1 and 8. At day 15, OA challenge was performed under cover of 10 mg/kg mepyramine (i.p.), and the respiratory resistance (Rrs) was measured by the oscillation method for 96 hrs after the OA challenge. Immediate bronchial response (IBR) was observed within a few minutes and this was followed by 2 or 3 phase LBR that peaked at 6-8 hrs and 24 hrs after the OA challenge. The histamine concentration of bronchoalveolar lavage fluid (BALF) was significantly increased during the IBR after the antigen challenge (p<0.05) . Airway responsiveness to inhaled acetylcholine (ACh) was increased significantly 48 hrs after the OA challenge (p<0.01) . Pretreatment with Ibudilast inhibited the increased airway responsiveness to ACh at 48 hrs after the OA challenge (p<0.05) and increased histamine concentration of BALF during IBR (p<0.1) . The results suggest that Ibudilast inhibits airway hyperresponsiveness 48 hrs after OA challenge in OA sensitized guinea pigs.