IN-VIVO CHARACTERIZATION OF THE ANTIINFLAMMATORY EFFECT OF CYCLOSPORINE-A ON HUMAN BASOPHILS

We investigated whether cyclosporin A (CsA) in vivo exerts anti-inflam matory effects by inhibiting IgE- and non-IgE-dependent mediator relea se from human basophils. Six healthy volunteers were given oral CsA (5 mg/kg twice daily) or placebo for 5 days. Plasma CsA and basophil rel easability in response to anti-IgE, FMLP, and A23187 were monitored 1 day before treatment, on alternate days during the treatment course, a nd 1 and 8 days after cessation of treatment. A constant plasma level of approximately 250 ng/ml CsA was obtained during CsA treatment. Baso phil releasability in response to anti-IgE, FMLP, and A23187 was dimin ished by 20 to 60% throughout the course of CsA treatment. Placebo had no effect on basophil releasability. There was a significant correlat ion between plasma CsA and the decrease of histamine release induced b y anti-IgE (r(s) = -0.66; p < 0.0005), FMLP (r(s) = -0.59; p < 0.001) and A23187 (r(s) = -0.68; p < 0.0001). In a second study, eight normal volunteers were given a single oral dose of CsA (7 mg/kg) or placebo, and plasma CsA and basophil releasability were monitored at different times thereafter. A rapid and significant reduction of histamine rele ase induced by anti-IgE, FMLP, and A23187 paralleled a sharp increase of CsA plasma levels, which peaked at 5 h and lasted approximately 13 h. This study indicates that oral administration of CsA in normal subj ects causes a rapid and significant inhibition of histamine release fr om basophils. This is the first evidence that in vivo administration o f CsA can modulate the release of proinflammatory mediators from basop hils obtained ex vivo.