The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma.
BACKGROUND
Apoptosis may be important in limiting airway eosinophilia. Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum.


OBJECTIVE
To assess the effect of montelukast on eosinophil apoptosis in a group of patients with mild persistent asthma (MPA) and to compare this effect with the apoptotic effect of fluticasone propionate (FP).


METHODS
Randomly selected patients with MPA (n = 22) who had not taken anti-inflammatory therapy within the preceding 12 months were included in the study. The sputum induction procedure was performed and the patients were divided into two groups: group 1 (n = 10) received FP 250 microg/day and group 2 (n = 22) received montelukast 10 mg/day orally for 4 weeks. Sputum induction was repeated after the treatment period. The resulting cytospin slides were stained by Wright's stain and morphologic changes in apoptotic eosinophils were assessed by the use of light microscopy by two blinded expert pathologists. Serum soluble Fas ligand (sFasL) concentrations were measured by an ELISA method at baseline and after treatment in both groups, as well as in a group of healthy subjects.


RESULTS
In within-group comparisons, the apoptotic ratio (AR) increased at the end of the study period in group 1 (p = 0.05). In the group treated with FP the ratio of sputum eosinophils significantly decreased (p = 0.02), and the AR significantly increased (p < 0.005). No differences were found in the two study groups in serum sFasL levels at the end of the treatment period compared with baseline values (p > 0.05).


CONCLUSIONS
Our findings demonstrate that 4 weeks' treatment with a CysLT receptor antagonist (montelukast) resulted in an increase in eosinophil apoptosis comparable to that produced by FP, suggesting that induction of apoptosis may be a potential mechanism for the mode of action of CysLT receptor antagonists in asthma.
Abadoglu
O
O
Department of Chest Diseases, Division of Allergy, Ankara University School of Medicine, Cebeci Hospital, Civas, Ankara, Turkey. ozabadoglu@hotmail.com
Mungan
D
D
Aksu
O
O
Erekul
S
S
Misirligil
Z
Z
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003521:Cyclopropanes; D004802:Eosinophilia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D015588:Observer Variation; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D013183:Sputum / Q000166:cytology*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D020024:Leukotriene Antagonists; D008562:Membrane Glycoproteins; D011804:Quinolines; D013440:Sulfides; D000068298:Fluticasone; C093875:montelukast