Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats.
We determined the effect of cyclosporine A (CSA) on airway reactivity and remodeling after chronic antigen challenge in Ascaris suum (AA)-sensitized cats. CSA efficacy was demonstrated by inhibition of interleukin-2 (IL-2) production from phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear (PBMN) cells. Twenty-four hours after the first AA exposure, cats not receiving cyclosporine (CsA-) demonstrated airway hyperresponsiveness (AHR) to acetycholine (approximately 1.0 log increase in PD200 versus baseline; p < 0.01), and a 13-fold increase in eosinophils in bronchoalveolar lavage fluid (BALF) (p < 0.01). AHR persisted (approximately 1.5 log increase in PD200 p < 0.001 versus baseline), and BALF eosinophilia was unchanged in CsA-cats 72 h after final AA challenge. The percent of normodense BALF eosinophils also decreased substantially in CsA-cats (p < 0.05). Necropsy specimens from CsA-cats demonstrated: (1) increased smooth-muscle thickness; (2) goblet cell and submucosal gland hypertrophy and hyperplasia; and (3) epithelial erosion with eosinophilic infiltration. There was no significant change in AHR, BALF, eosinophilia, or histology after chronic AA challenge in Csa-treated cats. These data suggest that CsA inhibits products of immune cells necessary for the development of AHR, airway inflammation, and airway wall remodeling caused by immune-sensitization in this model of atopic asthma.
Padrid
P A
PA
Asthma, Allergy and Immunology Disease Research Center, Department of Medicine, University of Chicago, IL 60637, USA.
Cozzi
P
P
Leff
A R
AR
D000109:Acetylcholine; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D017165:Ascaris suum / Q000276:immunology*; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002415:Cats; D016572:Cyclosporine / Q000494:pharmacology*; D004804:Eosinophils / Q000473:pathology; D005260:Female; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D013601:T-Lymphocytes / Q000378:metabolism
D000947:Antigens, Helminth; D007376:Interleukin-2; D016572:Cyclosporine; D000109:Acetylcholine