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) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p < 0.0005). We conclude that intratracheal administration of IL-1 beta induces the inflammatory changes, which are characterized by an increase in neutrophil counts in BALF, and increased AR to bradykinin, and that active sensitization per se does not potentiate the effect of IL-1 beta on AR to acetylcholine or bradykinin or on airway inflammation.
Tsukagoshi
H
H
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, England.
Sakamoto
T
T
Xu
W
W
Barnes
P J
PJ
Chung
K F
KF
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007114:Immunization; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D007375:Interleukin-1; D010047:Ovalbumin; D000109:Acetylcholine; D001920:Bradykinin