EFFECT OF INTERLEUKIN-1-BETA ON AIRWAY HYPERRESPONSIVENESS AND INFLAMMATION IN SENSITIZED AND NONSENSITIZED BROWN-NORWAY RATS

Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway. rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratr acheally. We examined animals 14 to 21 days after initial sensitizatio n at 18 to 24 hours after the intratracheal administration of IL-1 bet a. We evaluated AR to acetylcholine as -log PC200, which is -log(10) t ransformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increas e in lung resistance. BALF was examined as an index of inflammatory ch anges within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals chat w ere given IL-1 beta demonstrated a significant increase of AR to brady kinin at 18 to 24 hours and a significant increase of neutrophil count s in BALF, which was already observed by, 4 to 6 hours. There was a si gnificant correlation between AR to bradykinin and neutrophil counts i n BALF in all animals (r = 0.644; p < 0.0005). We conclude that intrat racheal administration of IL-1 beta induces the inflammatory changes, which are characterized by an increase in neutrophil counts in BALF an d increased AR to bradykinin, and that active sensitization per se doe s not potentiate the effect of IL-1 beta on AR to acetylcholine or bra dykinin or on airway inflammation.