In vivo characterization of the anti-inflammatory effect of cyclosporin A on human basophils.
We investigated whether cyclosporin A (CsA) in vivo exerts anti-inflammatory effects by inhibiting IgE- and non-IgE-dependent mediator release from human basophils. Six healthy volunteers were given oral CsA (5 mg/kg twice daily) or placebo for 5 days. Plasma CsA and basophil releasability in response to anti-IgE, FMLP, and A23187 were monitored 1 day before treatment, on alternate days during the treatment course, and 1 and 8 days after cessation of treatment. A constant plasma level of approximately 250 ng/ml CsA was obtained during CsA treatment. Basophil releasability in response to anti-IgE, FMLP, and A23187 was diminished by 20 to 60% throughout the course of CsA treatment. Placebo had no effect on basophil releasability. There was a significant correlation between plasma CsA and the decrease of histamine release induced by anti-IgE (rs = -0.66; p < 0.0005), FMLP (rs = -0.59; p < 0.001) and A23187 (rs = -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 release 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 subjects causes a rapid and significant inhibition of histamine release from basophils. This is the first evidence that in vivo administration of CsA can modulate the release of proinflammatory mediators from basophils obtained ex vivo.
Casolaro
V
V
Division of Clinical Immunology and Allergy, University of Naples Federico II, School of Medicine, Italy.
Spadaro
G
G
Patella
V
V
Marone
G
G
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016037:Single-Blind Method
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016572:Cyclosporine