The effect of formoterol on the late asthmatic phenomena in guinea pigs.
We investigated the effects of formoterol, a new, long-acting, selective beta 2-adrenoceptor agonist, on the antigen-induced late asthmatic response (LAR) and airway inflammation in guinea pigs. Animals were sensitized by exposure to aerosolized ovalbumin (2% in saline). After antigen challenge, preceded by administration of an H1-receptor antagonist, specific airway conductance was measured with a two-chambered whole-body plethysmograph. An aerosolized solution of formoterol, isoproterenol, or saline was inhaled 15 minutes before challenge. Bronchoalveolar lavage (BAL) was performed 24 hours after challenge. The provocative concentrations of histamine required to decrease specific airway conductance by 50% were obtained before challenge, at 24 hours, and at 72 hours after challenge. The LAR (52.7% +/- 7.7% of the baseline; p less than 0.02) was observed 6 to 8 hours after antigen challenge. An increased cellular influx in BAL (mainly eosinophils and macrophages) and an increased bronchial responsiveness to histamine occurred 24 hours after antigen challenge. Formoterol completely inhibited the LAR and the cellular increase in BAL; however, isoproterenol failed to prevent either the cellular infiltration or the LAR. Formoterol also decreased the antigen-induced increase in bronchial reactivity. These findings suggest that formoterol has inhibitory effects on the underlying inflammatory processes in antigen-induced asthma in addition to prolonged bronchodilation.
Allergic Disease Center, Creighton University, Omaha, Neb. 68178.
H
H
Sugiyama
C
C
Okada
A K
AK
Bewtra
R J
RJ
Hopp
R G
RG
Townley
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects; D007507:Therapeutic Irrigation; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000941:Antigens; D004983:Ethanolamines; D007545:Isoproterenol; D000068759:Formoterol Fumarate