Montelukast reduces eosinophilic inflammation by inhibiting both epithelial cell cytokine secretion (GM-CSF, IL-6, IL-8) and eosinophil survival.
Leukotriene receptor antagonists, such as montelukast (MK), are currently used to treat rhinitis and asthma, but their anti-inflammatory role in eosinophil inflammation is not well understood. The aim of this study is to investigate the effect of MK on an in vitro model of upper-airway eosinophil inflammation by reducing pro-inflammatory cytokines from both nasal mucosa (NM) and polyp (NP) epithelial cells and reducing eosinophil survival primed by epithelial cell secretions. Epithelial cells were stimulated with fetal bovine serum (FBS) with or without MK for 24 hours, and cytokine concentrations in epithelial secretions were measured by ELISA. After incubating peripheral blood eosinophils with epithelial cell-conditioned media (ECM) with or without MK up to 3 days, eosinophil survival was assessed by Trypan blue dye exclusion. Results are expressed as mean±SEM of cytokine concentration (percent of control) or eosinophil survival (percent). Epithelial cell stimulation increased GM-CSF, IL-6, IL-8, and sICAM-1 secretion in both NM and NP. MK had a significant inhibitory effect on FBS-induced GM-CSF, IL-6, and IL-8 secretion, but not sICAM-1, in both NM and NP. MK also showed an inhibitory effect (p<0.05) on ECM-induced eosinophil survival from both NM (from 10(-5)M to 10(-7)M, n=7) and NP (at 10(-5)M, n=7), after 3 days of incubation. These anti-inflammatory effects on epithelial cell cytokine secretion and on eosinophil survival suggest that montelukast may contribute to the reduction of eosinophilic inflammation in upper-airway inflammatory diseases such as rhinitis and nasal polyposis.
Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Catalonia. jmullol@clinic.ub.es
J
J
Mullol
F B
FB
Callejas
E
E
Méndez-Arancibia
M
M
Fuentes
I
I
Alobid
A
A
Martínez-Antón
A
A
Valero
C
C
Picado
J
J
Roca-Ferrer
D000085:Acetates / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes; D016207:Cytokines / Q000096:biosynthesis*; D004802:Eosinophilia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009298:Nasal Polyps / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011804:Quinolines / Q000494:pharmacology*; D012220:Rhinitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013440:Sulfides
D000085:Acetates; C508606:CXCL8 protein, human; D003521:Cyclopropanes; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C093875:montelukast