Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma.
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) and mite (M) allergens. In this study 18 patients with allergic asthma (nine women and nine men, aged 27-67 years) were evaluated. PBMCs from these patients were cultured for 24 hours in the presence of phytohemagglutinin (15 micrograms/mL), RW antigen E (0.39 U/mL), or M (16.8 micrograms/mL) allergens with (1, 10, 50 microM) 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 the RNA samples using beta-actin polymerase chain reaction primers for a control 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 microM of montelukast was noted in 5 patients with RW and in 10 patients with M. 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 1 of 11 patients. However, in seven of nine patients tested, IL-5 mRNA was induced by both RW and M, and montelukast at 10 microM 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.
Frieri
Marianne
M
Division of Allergy Immunology and Clinical Immunopathology, Department of Medicine and Pathology, Nassau University Medical Center, State University of New York at Stony Brook, Stony Brook, New York, USA.
Therattil
Jaya
J
Wang
Soo Fang
SF
Huang
Chien-Yiu
CY
Wang
Yung-Chih
YC
D000085:Acetates / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000485:Allergens / Q000009:adverse effects; D031164:Ambrosia / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D018929:Cell Culture Techniques; D003521:Cyclopropanes; D003545:Cysteine / Q000378:metabolism*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008925:Mites; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013440:Sulfides
D000085:Acetates; D000485:Allergens; D003521:Cyclopropanes; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D012333:RNA, Messenger; D013440:Sulfides; C112381:cysteinyl-leukotriene; D003545:Cysteine; C093875:montelukast