Effect of some immunosuppressors on allergic bronchial inflammation and airway hyperresponsiveness in mice.
The effects of two new immunosuppressors, FK-506 and mizoribine, on antigen-induced bronchial inflammation and reactivity to acetylcholine in mice were studied in comparison with those of cyclosporin A and cyclophosphamide. Three inhalations of an antigen by actively sensitized BALB/c mice resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (mononuclear cells and eosinophils) and the amount of interleukin 5 (IL-5) increased significantly. In BALB/c nu/nu mice (athymic mice), three inhalations of antigen caused no significant change in either airway inflammation or hyperresponsiveness. The administration of each of the four immunosuppressors clearly inhibited antigen-induced airway eosinophilia. Moreover, FK-506, mizoribine and cyclophosphamide clearly inhibited the antigen-induced IL-5 production and cyclosporin A showed the tendency to inhibit IL-5 production. Whereas FK-506, mizoribine and cyclosporin A clearly inhibited the antigen-induced airway hyperreactivity in BALB/c mice, cyclophosphamide did not show a significant effect on this airway hyperreactivity. These results indicate that FK-506, mizoribine and cyclosporin A, but not cyclophosphamide, inhibit antigen-induced airway hyperreactivity in mice. The mechanism which inhibits antigen-induced airway eosinophilia and IL-5 production is not involved in the inhibitory mechanism of airway hyperreactivity by FK-506 and mizoribine.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Yamaguchi
S
S
Tanaka
H
H
Inagaki
N
N
D000336:Aerosols; D000818:Animals; D001985:Bronchial Provocation Tests; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D006967:Hypersensitivity / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010047:Ovalbumin / Q000276:immunology; D012137:Respiratory System / Q000276:immunology*; D012263:Ribonucleosides / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
D000336:Aerosols; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D012263:Ribonucleosides; C010052:mizoribine; D016572:Cyclosporine; D003520:Cyclophosphamide; D010047:Ovalbumin; D016559:Tacrolimus