INHIBITORY EFFECT OF CYCLOSPORINE-A ON EOSINOPHIL INFILTRATION IN THE GUINEA-PIG LUNG INDUCED BY ANTIGEN, PLATELET-ACTIVATING-FACTOR AND LEUKOTRIENE B-4

The effect of the immunosuppressive compound, cyclosporin A, and the corticosteroid, betamethasone, was investigated on eosinophil accumulation in guinea-pig lung tissue induced by antigen; platelet-activating factor (PAF) and leukotriene B-4 (LTB(4)). The accumulation of eosinophils in the peribronchial area was evaluated on histological preparations. The lung sections were stained with Luna's reagent specific for eosinophil granule content. Oral treatment of the guinea-pigs with cyclosporin, 10 mg.kg(-1) three times a day for two days, and 10 mg.kg(-1) 1 h before antigen challenge, significantly reduced the accumulation of eosinophils observed at 4 and 24 h, in the peribronchial area of sensitized guinea-pig lung. Betamethasone (3 mg.kg(-1)), administered orally 24 h and 1 h before antigen challenge elicited a moderate but significant reduction of antigen-induced eosinophil accumulation. Pretreatment of the guinea-pigs with cyclosporin or betamethasone elicited a marked inhibition of the accumulation of eosinophils in the peribronchial area induced by aerosolized PAF (100 mu g.ml(-1)) or LTB(4) (5 mu g.ml(-1)). Since cyclosporin and betamethasone significantly inhibit the antigen-induced eosinophil accumulation, these results suggest that antigen-induced lung eosinophilia is dependent of T-lymphocytes. However, cyclosporin and betamethasone may also reduce the chemotactic activity of PAF and LTB(4) on guinea-pig eosinophils.