[Effect of montelukast sodium on TGF-beta(1) of peripheral blood mononuclear cells from children with mild persistent asthma].

OBJECTIVE

To investigate the role of transforming growth factor beta(1) (TGF-beta(1)) in the pathogenesis of bronchial asthma in children and assess the effect of montelukast sodium (leukotriene receptor antagonist) on TGF-beta(1) levels.

METHOD

A 12 weeks single-blind, placebo-controlled trail was conducted in 60 children with mild persistent asthma [aged 5 - 14 years, mean (7.10 ± 0.27) years]. Patients were randomly assigned to receive 5 mg montelukast sodium or placebo for 12 weeks. And 30 healthy control children [aged 5 - 14 years, mean (7.60 ± 0.25) years] were also recruited in this study from Sep. 2009 to Sep. 2010. Clinical effects and pulmonary function were evaluated before and 12 weeks after treatment. The mRNA expression of TGF-beta(1) in the peripheral blood mononuclear cells was detected by using RT-PCR with beta-actin as internal control. The percentage of the different subpopulations of Foxp(3)(+)CD4(+) T cells was assayed by 4-color flow cytometric analysis system and the levels of TGF-beta(1) in plasma by ELISA.

RESULT

(1) The basic characteristics between asthma group and healthy group had no significant difference. (2) Following treatment, there was significant increase in pulmonary function in asthmatic children. The effect in the group of montelukast sodium was superior to that of placebo group (P < 0.05). (3) The serum expression of TGF-beta(1) in asthmatic children was lower than that in control group (q = 20.01, P < 0.01); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (20.03 ± 1.14) ng/L for montelukast sodium group and (12.10 ± 3.91) ng/L for placebo group (P < 0.05). (4) The mRNA expression of TGF-beta(1) in asthma children was lower than that in control group (0.31 ± 0.07 vs 0.61 ± 0.2, q = 8.97, P < 0.05); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (0.46 ± 0.13) for montelukast sodium group and (0.32 ± 0.04) for placebo group (q = 8.25, P < 0.05). (5) It was shown that the total Foxp(3)(+)CD(4)(+) cell percentage was higher in asthmatic children than those of control group (8.30% ± 1.30% vs 6.05% ± 1.80%); the proportion of the three subpopulation was different between groups: CD(45) RA(+)Foxp(3)(lo) was higher in asthmatic group (4.60% ± 1.04% vs 3.27% ± 1.03%) and CD(45) RA(-)Foxp(3)(hi) was lower (0.75% ± 0.13% vs 0.93% ± 0.26%); while CD(45) RA(-)Foxp(3)(lo) had no significant difference among groups (2.40% ± 0.83%, 1.61% ± 1.10%). After 12 weeks of treatment, the percentage of CD(45) RA(-)Foxp(3)(hi) was increased in montelukast sodium group compared with placebo group (1.16% ± 0.24% vs 0.89% ± 0.22%). (6) Spearman correlation analysis revealed that TGF-beta(1) levels had no correlation with the levels of pulmonary function.

CONCLUSION

The protein and mRNA expression level of TGF-beta(1) was low in those asthmatic children. Insufficient secretion of TGF-beta(1) and the defective ability of activated regulatory T cells (CD(45) RA(-)Foxp(3)(hi)) in Foxp(3)(+)CD(4)(+) Treg cells might play an important role in pathogenesis of asthma. Up-regulation of the expression of TGF-beta(1) and induction of the expression of CD(45) RA(-)Foxp(3)(hi) in Foxp(3)(+)CD(4)(+)Treg cells by montelukast sodium may be one of the immunomodulatory mechanisms in asthma.