Inhibition of mediator release from dispersed nasal polyp cells by cyclosporin A.
The mechanisms of action of cyclosporin A require further elucidation since this drug includes anti-inflammatory properties unrelated to its previously documented effect of T cells. A study was performed using enzymatically dispersed cells from nasal polyps of 7 subjects to examine the effects of cyclosporin A on the release of histamine, leukotriene C4/D4 (LTC4/D4) and thromboxane (TxB2) following stimulation by anti-IgE. Cells were resuspended and preincubated with cyclosporin A (0.1, 1 and 10 microM) or 0.1% DMSO (the vehicle used to dissolve cyclosporin A) for 20 min prior to challenge with 10 microgram/ml epsilon-chain-specific anti-IgE for 45 min at 37 degrees C. Histamine, LTC4/D4 and TxB2 were measured using EIA. Cyclosporin A significantly inhibited the release of histamine, LTC4/D4, and TxB2 in a concentration-dependent manner. IC30 values, histamine (5.1 microM), LTC4/D4 (7.8 microM) and TxB2 (6.2 microM), were determined. These data demonstrate new antiallergic properties of cyclosporin A using a novel in vitro model which mimics more closely allergic inflammation.
Montpellier-Asthme and INSERM U 454, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire, Montpellier, France.
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Lebel
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Campbell
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Bousquet
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000276:immunology* / Q000378:metabolism; D009298:Nasal Polyps / Q000276:immunology* / Q000473:pathology; D013929:Thromboxane B2 / Q000276:immunology* / Q000378:metabolism
D007166:Immunosuppressive Agents; D017997:Leukotriene C4; D013929:Thromboxane B2; D016572:Cyclosporine