Effect of inhaled cyclosporin A on the allergen-induced late asthmatic response and increased in airway hyperresponsiveness in a guinea pig model of asthma.
Oral administration of cyclosporin (CsA), a potent inhibitor of helper T cell function, prevents the allergen-induced late asthmatic response (LAR) and the increase in airway hyperresponsiveness (AH) seen in actively sensitized guinea pigs. The systemic administration of this agent in humans has been associated with serious side effect, therefore, the effects of inhaled CsA were therefore examined in guinea pigs that were actively sensitized by repeated exposure to nebulized ovalbumin. Respiratory resistance (Rrs) of the animals was measured by an oscillation method and the extent of AH was inferred from the inhaled concentration of histamine required to increase Rrs by 200%. The magnitude of ovalbumin-induced immediate bronchoconstriction after sensitization was similar in CsA-treated and nontreated control animals. However, a LAR was observed in 4/5 control animals but in 0/5 CsA-treated animals. The increase in AH observed 24 hours after antigen exposure in control animals was significantly inhibited by prior CsA inhalation. Significant CsA concentrations were detected by radioimmunoassay in the lungs of CsA-treated animals. Thus, inhaled CsA should be further investigated because it may be useful treating asthma while avoiding side effects.
Arima
M
M
Department of Allergy and Clinical Immunology, Dokkyo University School of Medicine.
Yukawa
T
T
Terashi
Y
Y
Makino
S
S
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000517:prevention & control*; D008297:Male
D000485:Allergens; D016572:Cyclosporine