Am. J. Respir. Crit. Care Med., Vol 154, No. 6, 12 1996, 1812-1818.
Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats
PA Padrid, P Cozzi and AR Leff
Asthma, Allergy and Immunology Disease Research Center, Department of Medicine, University of Chicago, IL 60637, USA.
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.
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Copyright © 1996 American Thoracic Society
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