1. ¹Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637
2. ²Committee on Comparative Medicine and Pathology, The University of Chicago, Chicago, IL 60637
3. ³Committee on Immunology, The University of Chicago, Chicago, IL 60637
4. ⁴Committee on Cellular Physiology and Clinical Pharmacology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637
5. ⁵Eli Lilly Co., Indianapolis, IN 46285, U.S.A.

Correspondence: Philip A Padrid, Department of Medicine, MC 6076, Section of Pulmonary and Critical Care Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A.

Received 10 September 1997; Revised 21 November 1997; Accepted 8 December 1997.

Abstract

1. We determined the effect of cyclosporine A (CsA) treatment on mast cell degranulation and lung resistance (R_L) in vivo, and tracheal smooth muscle (TSM) contraction ex vivo after antigen challenge in sensitized cats. We also determined the direct effects of addition of CsA to the tissue bath on antigen-induced responses of TSM in vitro.
2. Cats (n=10) were sensitized by i.m. injection of Ascaris suum antigen (AA); 5 cats (CsA+) received CsA twice daily for 2 weeks before acute antigen challenge in doses sufficient to suppress interleukin-2 secretion from feline peripheral blood mononuclear cells ex vivo.
3. Lung resistance increased comparably within 10 min of exposure to AA (P<0.03). Histamine content in bronchoalveolar lavage fluid from both groups increased comparably within 30 min of antigen challenge, from undetectable levels to 54274 pg ml^-1 post AA for CsA+ and from 7419 pg ml^-1 at baseline, to 970180 pg ml^-1 post AA CsA- (P<0.05; P=NS vs CsA+).
4. In excised TSM, active tension elicited by exposure to AA in vitro was 10738% KCl in the CsA+ group vs 14456% KCl in the CsA- group (P=NS). However, contraction of TSM (n=4) harvested from both groups was abolished or greatly diminished after AA challenge when tissues were pre-incubated with 1 M CsA in vitro (88% KCl, P<0.05 vs CsA+ and CsA-). This was associated with inhibited release of 5-hydroxytryptamine into the organ bath fluid of tissues treated with CsA in vitro only.
5. We demonstrated that CsA treatment in vivo does not inhibit the early phase asthmatic response or mast cell degranulation following antigen challenge in sensitized cats. Additionally, the effects of CsA on mast cell function ex vivo do not reflect lack of effects of CsA on mast cell function in vivo in this animal model of atopic asthma.