Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma
Frieri, M.; Therattil, J.; Wang, S.Fang.; Huang, C-Yiu.; Wang, Y-Chih.
Allergy and Asthma Proceedings 24(5): 359-366
2003
ISSN/ISBN: 1088-5412 PMID: 14619337 Document Number: 558839
Important in the pathogenesis of asthma is the secretion of interleukin (IL)-5 by allergen-specific TH2 cells, which augments eosinophil functions, as well as subsequent synthesis of cysteinyl leukotrienes (CysLTs). Montelukast is an inhibitor of CysLT and also has been shown to decrease eosinophil counts in peripheral blood and sputum of patients with asthma. This study was performed to investigate the in vitro effects of montelukast, a leukotriene receptor antagonist, on CysLTs and IL-5 production and expression by peripheral blood mononuclear cells (PBMCs) stimulated with ragweed (RW) [Ambrosia] and mite (M) allergens. 18 patients with allergic asthma (9 women and 9 men, aged 27-67 years) were evaluated [New York, USA]. PBMCs from these patients were cultured for 24 h in the presence of phytohaemagglutinin (15 micro g/ml), RW antigen E (0.39 micro g/ml) or M (16.8 micro g/ml) allergens with (1, 10, 50 micro M) and without montelukast. Enzyme-linked immunosorbent assay was used to measure the concentration of CysLTs, regulated upon activation normal T-cell expressed and secreted (RANTES), and IL-5 in the culture supernatants, and total RNA was extracted from the cultured PBMCs. Reverse transcription-polymerase chain reaction was performed on RNA samples using beta -actin polymerase chain reaction primers for controls and IL-5 specific primers for detecting IL-5 mRNA expression in the cells. Elevated CysLT levels were noted in 8 of 18 patients with RW (range, 8-580 pg/ml) and in 13 of 18 patients with M (range, 7-1613 pg/ml). Inhibition of CysLTs by 10 micro M of montelukast was noted in 5 patients with RW and in 10 patients with M. The levels of RANTES in some patients were increased by both allergens without consistent inhibitory effects of montelukast. IL-5 secretion measured by enzyme-linked immunosorbent assay was detected in only one of 11 patients. However, in 7 of 9 patients tested, IL-5 mRNA was induced by both RW and M, and montelukast at 10 micro M completely blocked IL-5 mRNA expression. Therefore, montelukast may be anti-inflammatory by inhibiting IL-5 mRNA expression and reducing CysLT secretion by PBMCs from asthmatic patients.