Influência do montelucaste sobre o estado de ativação dos eosinófilos e função dos fagócitos em crianças asmáticas

AUTOR(ES)

Valéria Botan Gonçalves

DATA DE PUBLICAÇÃO

2010

RESUMO

Asthma is one of the most common chronic diseases in childhood and its prevalence and severity are increasing in many parts of the world in recent years. The main characteristic of asthma is inflammation of the lower airways, responsible for bronchial hyperresponsiveness and variable airflow limitation, reversible with or without treatment. Several cells play an important role in inflammation as eosinophils, neutrophils and monocytes. In asthma, the leukotrienes are implicated in multiple physiopathological mechanisms including mucus hypersecretion, increased microvascular permeability, impaired ciliary activity, recruitment of inflammatory cells, edema and neuronal dysfunction. It was shown that montelukast, antileukotriene, is able to inhibit the production of proinflammatory cytokines, decreasing chemotaxis and half-life of eosinophils. However, the influence of montelukast on the activation of eosinophils and phagocytic functions of monocytes and neutrophils in asthmatic subjects are not clear yet. Therefore, the objective of this work was to evaluate the effect of montelukast on the state of activation of eosinophils, the phagocytic capacity of neutrophils and monocytes and the production of free radicals by phagocytes in children with persistent asthma. It was selected 83 asthmatic children that were randomly assigned to treatment with montelukast or placebo for 12 weeks and 10 healthy control children. Peripheral blood (1 to 10 ml) was taken from the children after parents informed consent. The state of activation of peripheral blood eosinophils was assessed by their morphological parameters after adherence to slide, before and after 12 weeks of treatment with montelukast or placebo. The following morphological parameters were evaluated: normal eosinophils, spreading, rounding, presence of localized and generalized pseudopods, release of small, moderate and large quantity of granules, cytoplasmatic vacuoles, cluster of free eosinophils granules, cell degeneration and cell communication. The monocyte and neuthrophil phagocytic capacity were assessed through pathogen-associated molecular patterns receptors (PAMPr) and through opsonin receptors. The phagocytic index was calculated as the average number of ingested Saccharomyces cerevisiae per phagocyte multiplied by the percentage of cells engaged in phagocytosis. The oxidative capacity was assayed by the nitroblue tetrazolium (NBT) test. The number of eosinophils with normal feature in peripheral blood showed an inverse correlation with the severity of asthma, while the emission of widespread pseudopods and isolated granules showed positive correlation with the severity of asthma. Treatment with montelukast was able to reduce the number of eosinophils in peripheral blood, and to increase the proportion of eosinophils with normal feature. The drug was also able to decrease the proportion of eosinophils with rounded feature and that releasing free eosinophil granules after 12 weeks of treatment compared to placebo. There was no difference in the percent reduction of NBT dye between asthma individuals and healthy controls before starting treatment, but individuals with asthma showed a stronger reduction of NBT than the healthy one. After 12 weeks of treatment with montelukast, there was a decrease in the power of reduction in both groups treated with placebo or montelukast. The neutrophil phagocytic index through pathogen-associated molecular patterns receptors in asthma individuals was lower than that of healthy control individuals. Montelukast treatment decreased the phagocytic index of monocytes through opsonin receptors when compared to placebo. Our data showed, for the first time, that montelukast is able to modify the activation of eosinophils correlated with clinical severity and that the method used to assess eosinophil activation is accurate, easy to perform and can be a marker of inflammation in asthma, and it could be used to the follow up of treatment of asthma individuals.

ASSUNTO(S)

asma eosinófilos montelucaste medicina

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