Comparative effects of a glucocorticosteroid, theophylline and the peptido-leukotriene-antagonist CGP 45715A on antigen-induced early and late phase airway response and inflammatory cell influx in sensitised guinea pigs

A novel model of allergic early and late-phase reaction in the airways of c onscious guinea pigs was developed and the effect of established and novel antiasthmatic drugs on peak of immediate response, late phase response and associated inflammatory cell influx investigated. Guinea pigs were sensitis ed twice in adjuvant (50 mg/kg silica + 0.1 ml/kg Bordetella pertussis). Un der cover of 10 mg/kg i.p. mepyramine guinea pigs exhibited still a pronoun ced immediate reaction. During a screening phase about 75% of guinea pigs d emonstrated a late phase reaction of decrease of tidal volume between 4-10 h after ovalbumin inhalation. In a cross over study theophylline at 50 mg/k g p.o. (-1 h before ovalbumin) tended to attenuate not only the peak of the immediate reaction by about 69% (P > 0.05, n = 12), but inhibited the airw ay late phase response significantly (P < 0.05, 5-10 h, n = 12). Methylpred nisolone (40 mg/kg p.o. 1 h before ovalbumin) did not inhibit the immediate response, but the late phase response. In contrast the cysteinyl-leukotrie ne antagonist CGP 45715A (Iralukast; 30 mg/kg p.o. 2 h before ovalbumin) ne ither interfered with the peak of the immediate, nor with the late phase re sponse. When bronchoalveolar lavage by orotracheal route was performed 24 h after ovalbumin inhalation, total cell count, eosinophils, neutrophils, ma crophages and lymphocytes were significantly increased in ovalbumin-control s compared to sham (n = 5; P < 0.05), Methylprednisolone reduced significan tly the antigen-induced increase of total cell count and eosinophil number. Neither theophylline nor the cysteinyl-leukotriene receptor antagonist att enuated the antigen-associated cell influx. The results do not provide evid ence for a major role of cysteinyl-leukotrienes in the late phase response and inflammatory cell influx in this model. (C) 1999 Elsevier Science B.V. All rights reserved.