Inhibition of histamine release from human lung and rat peritoneal mast cells by cyclosporin-A.
Cyclosporin A (CS-A) partly inhibited IgE-mediated histamine release from human lung tissue in vitro (chopped and collagenase-dispersed preparations). Inhibition started at concentrations within the clinical blood level of the drug, but the IC50 was much higher (10-50 microM; 50% inhibition reached only in some experiments). CS-A also inhibited histamine release from rat peritoneal mast cells (RPMC) induced by antigen, concanavalin-A (Con-A), compound 48/80 and ionophore A23187. The IC50 values were 0.3, 23.0, and 33.0 microM for Con-A, A23187 and ovalbumin respectively. Inhibition of 48/80-induced release did not reach 50%. By comparison with human basophils the human lung and RPMC were less sensitive to the inhibitory action of CS-A. The IgE-mediated Schultz-Dale reaction in human lung strips was slightly and inconsistently inhibited by CS-A, but IgG1-mediated reaction in guinea-pig lung strips was potentiated by the drug.
Department of Pharmacology, University College London, UK.
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D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D007073:Immunoglobulin E