| Popis: |
Background: Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. Objective: To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Methods: Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 mu mol/L) and substance P (1 mu mol/L) with or without pretreatment with RUP (2.5 and 25 mu mol/L), which was added 10 minutes before stimulation. Release of beta-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. Results: PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 mu mol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 mu mol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 mu mol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. Conclusion: PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
