Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge 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 phytohemagglulinin (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 (similar to 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 (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 challenge. The percent of normodense BALF eosinophils also decreased substantially in CsA- cats fp < 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, eosinaphilia, 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.