EARLY AND LATE-PHASE BRONCHOCONSTRICTIONS IN CONSCIOUS SENSITIZED GUINEA-PIGS AFTER MACROSHOCK AND MICROSHOCK INHALATION OF ALLERGEN AND ASSOCIATED AIRWAY ACCUMULATION OF LEUKOCYTES

Guinea-pigs were sensitized by i.p. injection of 10 mu g OA and 100 mg aluminium hydroxide in 1 ml normal saline. Fourteen to twenty-one day s after sensitization, animals were exposed to macroshock (1% OA for 2 min) or microshock (0.01% for 60 min) inhalation challenges with OA. Animals were protected against fatal anaphylaxis in the case of macros hocks with mepyramine (30 mg/kg i.p.) 30 min before exposure. Specific airway conductance (sG(aw)) was measured in conscious animals by whol e body plethysmography at intervals up to 72 h after challenge. An ear ly phase bronchoconstriction peaked significantly (P < 0.05) at 15 min after both macroshock and microshock OA exposures, with maximum falls in sG(aw) of 70.8 +/- 3.8 and -40.0 +/- 5.9%, respectively. These had resolved after 5 h. A late phase bronchoconstriction peaked variably between 17 and 24 h: the mean peak falls in sG(aw) after the macro- an d microshock challenges were significantly different from baseline (P < 0.05), at -21.6 +/- 3.7 and -38.0 +/- 3.9%, respectively. Control ex posures of OA-sensitized guineapigs to saline for either 2 or 60 min, in place of OA, produced no significant variation in sG(aw) values ove r the predicted early and late phases. Bronchoalveolar lavage (BAL) pe rformed at 5 or 24 h after OA challenge revealed significant increases in total cell numbers (P < 0.05) at 5 and 24 h after the OA macroshoc k challenge and at 24 h after the microshock, compared with saline cha llenges. Differential cell counts showed a significant (P < 0.05) incr ease in the proportion of neutrophils at 5 h and of neutrophils and eo sinophils at 24 h after the macroshock exposure to OA, compared with s aline controls. A significant (P < 0.05) increase in the proportion of eosinophils also occurred in BAL fluid at 24 h after microshock OA ch allenge. Neutrophils, however, did not alter at 24 h, yet a late phase bronchoconstriction was recorded. Thus, macroshock (with mepyramine c over) and microshock (without mepyramine cover) OA challenges result i n both early and late phase bronchoconstrictions. The late phase is as sociated with influx of eosinophils in both models but neutrophils onl y appear after the macroshock, indicating that late phase responses ma y not involve neutrophil infiltration to the airways. Copyright (C) 19 96 International Society for Immunopharmacology