Treatment of asthmatic patients with a cysteinyl leukotriene receptor-1 antagonist montelukast (Singulair), decreases the eosinophil survival-enhancing activity produced by peripheral blood mononuclear leukocytes in vitro.
BACKGROUND
Montelukast (Singulair, MSD) has been shown to have a beneficial effect on the clinical symptoms of asthma. We aimed to investigate the effect of montelukast treatment on the production of eosinophil survival-enhancing cytokines by peripheral blood mononuclear cells (PBMNC).


METHODS
PBMNC obtained from 15 grass-allergic patients (7 treated with montelukast and 8 with a placebo) were cultured for 72 h. Eosinophils from allergic patients were cultured with MNC supernatants alone or with addition of neutralizing antibodies, and the proportion of living cells was assessed by flow cytometry. In another experiment PBMNC from 6 allergic patients were cultured in vitro in the presence of montelukast or vehicle. Following stimulation the production of GM-CSF in monocytes was assessed.


RESULTS
Eosinophil survival in the MNC supernatants from the placebo-treated patients was significantly (P < 0.05) higher than in supernatants from montelukast-treated patients. GM-CSF was the predominant cytokine responsible for the eosinophil survival-enhancing activity (ESEA). In vitro production of GM-CSF by allergen-stimulated monocytes was significantly suppressed by addition of montelukast.


CONCLUSIONS
Treatment of patients with montelukast decreased the production of MNC-derived cytokines, particularly GM-CSF. We suggest that cysteinyl leukotriene receptor-1 (CysLT-R1) antagonists may act, at least partially, by diminishing the production of GM-CSF from PBMNCs.
D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018849:Controlled Clinical Trials as Topic; D003521:Cyclopropanes; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011804:Quinolines / Q000627:therapeutic use*; D018077:Receptors, Leukotriene / Q000627:therapeutic use*; D013194:Staining and Labeling; D013223:Statistics as Topic; D013440:Sulfides; D013997:Time Factors; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D016207:Cytokines; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C093875:montelukast