The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma

Apoptosis may be important in limiting airway eosinophilia. Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum. 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). 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 μg/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. 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). 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. La apoptosis puede ser importante para limitar los eosinfilos de las v as respiratorias. El tratamiento con antagonistas de los leucotrienos reduce el nmero de eosin filos tanto en la sangre perifrica como en el esputo. Evaluar el efecto del montelukast (M) sobre la apoptosis eosinof lica en un grupo de pacientes con asma leve persistente (ALP) para compararlo con el efecto apopttico del propionato de fluticasona (PF). Para el estudio se seleccionaron aleatoriamente pacientes con ALP (n = 22) que no haban recibido terapia antiinflamatoria durante los 12 meses previos. Tras proceder a la inducci n del esputo, los pacientes se dividieron en dos grupos: uno recibi 250 μg/d a de propionato de fluticasona (grupo 1, n = 10) y el otro 10 mg/da de M por v a oral (grupo 2, n = 12) durante 4 semanas. Tras el perodo de tratamiento se repiti la induccin del esputo. Los preparados resultantes obtenidos por citocentrifugaci n se tieron con colorante de Wright y dos pat logos expertos que desconocan el origen de las muestras las observaron al microscopio de luz para evaluar los cambios morfol gicos de los eosinfilos apopt ticos. Se midieron las concentraciones sricas del ligando Fas soluble (sFasL) mediante el m todo ELISA antes y despus del tratamiento en ambos grupos, midi ndose simultneamente en un grupo de sujetos sanos. Comparando los resultados en un mismo grupo, el ndice apopttico (IA) aument al final del perodo de estudio en el grupo 1 (p = 0,05). En el grupo tratado con PF, el indice de eosinfilos en el esputo disminuy significativamente (p = 0,02), mientras que hubo un aumento significativo del IA (p < 0,005). Los niveles s ricos de sFasL no variaron al final del perodo de tratamiento en comparaci n con los niveles iniciales en ambos grupos de estudio (p > 0.05). Nuestros hallazgos demuestran que un tratamiento de cuatro semanas con un antagonista de los receptores de Cis-LT, el montelukast, produce un aumento de la apoptosis eosinof lica comparable al que produce el propionato de fluticasona, lo que sugiere que la induccin de la apoptosis puede ser un mecanismo de accin de los antagonistas de los receptores de Cis-LT en el asma.