Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats

• Published in: American journal of respiratory and critical care medicine Vol. 154; no. 6 Pt 1; p. 1812
• Main Authors: Padrid, P A, Cozzi, P, Leff, A R
• Format: Journal Article
• Language: English
• Published: United States 01.12.1996
• Subjects: Acetylcholine; Animals; Antigens, Helminth - administration & dosage; Antigens, Helminth - immunology; Ascaris suum - immunology; Bronchi - pathology; Bronchial Hyperreactivity - chemically induced; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; Cats; Cyclosporine - pharmacology; Eosinophils - pathology; Female; Immunization; Interleukin-2 - biosynthesis; Leukocyte Count; Lymphocyte Activation - drug effects; Male; T-Lymphocytes - metabolism
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.154.6.8970375

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.