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

The effect of the immunosuppressive compound, cyclosporin A, and the c orticosteroid, betamethasone, was investigated on eosinophil accumulat ion in guinea-pig lung tissue induced by antigen; platelet-activating factor (PAF) and leukotriene B-4 (LTB(4)). The accumulation of eosinop hils in the peribronchial area was evaluated on histological preparati ons. The lung sections were stained with Luna's reagent specific for e osinophil granule content. Oral treatment of the guinea-pigs with cycl osporin, 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 se nsitized guinea-pig lung. Betamethasone (3 mg.kg(-1)), administered or ally 24 h and 1 h before antigen challenge elicited a moderate but sig nificant reduction of antigen-induced eosinophil accumulation. Pretrea tment of the guinea-pigs with cyclosporin or betamethasone elicited a marked inhibition of the accumulation of eosinophils in the peribronch ial area induced by aerosolized PAF (100 mu g.ml(-1)) or LTB(4) (5 mu g.ml(-1)). Since cyclosporin and betamethasone significantly inhibit t he antigen-induced eosinophil accumulation, these results suggest that antigen-induced lung eosinophilia is dependent of T-lymphocytes. Howe ver, cyclosporin and betamethasone may also reduce the chemotactic act ivity of PAF and LTB(4) on guinea-pig eosinophils.