CYCLOSPORINE-A INHIBITS AIRWAY REACTIVITY AND REMODELING AFTER CHRONIC ANTIGEN CHALLENGE CATS

We determined the effect of cyclosporine A(CSA) on airway reactivity a nd remodeling after chronic antigen challenge in Ascaris suum (AA)-sen sitized cats, CSA efficacy was demonstrated by inhibition of interleuk in-2 (IL-2) production from phytohemagglulinin (PHA)-stimulated periph eral blood mononuclear (PBMN) cells. Twenty-four hours after the first AA exposure, cats not receiving cyclosporine (CsA-) demonstrated airw ay hyperresponsiveness (AHR) to acetycholine (similar to 1.0 log incre ase in PD200 versus baseline; p < 0.01), and a 13-fold increase in eos inophils in bronchoalveolar lavage fluid (BALF) (p < 0.01). AHR persis ted (similar to 1.5 log increase in PD200 p < 0.001 versus baseline), and BALF eosinophilia was unchanged in CsA- cats 72 h after final AA c hallenge. The percent of normodense BALF eosinophils also decreased su bstantially in CsA- cats fp < 0.05). Necropsy specimens from CsA-cats demonstrated: (1) increased smooth-muscle thickness; (2) goblet cell a nd submucosal gland hypertrophy and hyperplasia;and (3) epithelial ero sion with eosinophilic infiltration. There was no significant change i n AHR, BALF, eosinaphilia, or histology after chronic AA challenge in Csa-treated cats. These-data suggest that CsA inhibits products of imm une cells necessary for the development of AHR, airway inflammation, a nd airway wall remodeling caused by immune-sensitization in this model of atopic asthma.