EFFECT OF INHALED CYCLOSPORINE ON THE RAT AIRWAY - HISTOLOGIC AND BRONCHOALVEOLAR LAVAGE ASSESSMENT

Airway inflammation plays a pivotal role in asthma. Over the last 10 y ears, evidence has accumulated for the potential role of lymphocytes i n airway inflammation. Since cyclosporin A (Cyc-A) can profoundly infl uence lymphocyte activation, it is appropriate to consider this drug a s a novel antiasthmatic. The effect of inhalation of low doses of Cyc- A on airway inflammation remains unclear. The purpose of this study wa s to investigate the bronchoalveolar lavage (BAL), peripheral blood ce ll profiles, and lung biopsy specimens in Cyc-A-pretreated rats. Twent y-nine rats (8 controls, 10 ovalbumin sensitized, and 11 Cyc-A inhalin g and ovalbumin sensitized) were included in the study. A commercial i ntravenous Cyc-A solution was given as a single dose of 20 mg/kg 1 h p rior to inhalation of ovalbumin via nebulizer. The total number of BAL cells significantly increased in rats inhaling Cyc-A when compared wi th ovalbumin-sensitized rats (2.37 +/- 2.34 x 10(6)/ml and 1.01 +/- 0. 49 x 10(6)/ml respectively, p < 0.05). There was a significant increas e in the percentage of lymphocytes (14.5 +/- 8.5 versus 27.4 +/- 7.4%, p < 0.03), a nonsignificant increase in the percentage of eosinophils (0.8 +/- 1.0 versus 3.0 +/- 4.6%), and a significant decrease in the percentage of polymorphonuclear leukocytes (9.4 +/- 6.9 versus 3.4 +/- 3.8%, p < 0.01) and macrophages (75.4 +/- 5.1 versus 50.2 +/- 11.8%, p < 0.02) in BAL in the ovalbumin-sensitized group as compared with co ntrols. Differential cell counts revealed a higher percentage of neutr ophils and macrophages in the BAL of Cyc-A-pretreated rats than in tha t of the ovalbumin-sensitized group (26.3 +/- 26.8 versus 3.4 +/- 3.8% , p < 0.01 and 66.1 +/- 7.7 versus 50.2 +/- 11.8%, p < 0.02). There wa s a nonsignificant decrease of lymphocytes and eosinophils in the Cyc- A-pretreated group when compared with the ovalbumin-sensitized group ( 27.4 +/- 7.4 versus 21.1 +/- 12.4 and 3.0 +/- 4.6% versus 2.4 +/- 2.6% ). The peripheral blood total white blood cell count decreased in the ovalbumin-sensitized and Cyc-A-pretreated groups as compared with the control group (2,520 +/- 1,098/mm(3), 3,591 +/- 2,251/mm(3), and 5,975 +/- 2,787/mm(3), respectively, p < 0.01). Tn addition, peripheral eos inophilia was detected in the Cyc-A-pretreated group when compared wit h controls and the ovalbumin-sensitized group (6.9 +/- 4.7, 2.4 +/- 1. 1, and 2.6 +/- 2.4%, respectively, p < 0.01). Light-microscopic examin ation of the airways revealed prominent eosinophilia in tracheal, bron chial, and bronchiolar sections in the ovalbumin-sensitized group: cou nts were 1.8 +/- 2.3/HPF, 10.3 +/- 11.4/HPF, 63.3 +/- 45.0/HPF, respec tively. Cyc-A resulted in a decrease of the eosinophil counts/HPF to O /HPF in trachea (p < 0.05), to 4.3 +/- 9.4/HPF in bronchi (p < 0.02), to 19.4 +/- 38.4 in bronchioles (p < 0.004). In conclusion, the presen t study supports the theory that locally administered inhaled low-dose Cyc-A is effective on inflammatory cells of sensitized airways and pe ripheral cells. It may therefore be useful in elucidating the inflamma tory mechanisms involved in asthma.