Effect of leukotriene receptor antagonist on expression and variation of TGF-beta in T lymphocyte for mild persistent asthma in children

Abstract

Objective: To investigate the role of TGF-β₁ and action of montelukast (MT) in the pathogenesis of asthma in children.

Methods: A single-blind, placebo-controlled trail was conducted in 60 mild persistent asthma children (5-14 y). Patients were randomly assigned to receive 5mg MT or placebo for 12 weeks. 30 healthy children (5-14 y) were as control. Clinical and pulmonary function were assessed before and after treatment. The mRNA expression of TGF-β₁ in PBMC cells, subtypes of FoxP₃⁺CD₄⁺ T cells and TGF-β₁ in plasma were measured.

Result: After treatment, symptomes were improved with signigicant increase in pulmonary function in asthmatic, MT superior to placebo (p<0.05). The mRNA expression of TGF-β₁ and TGF-β₁ level in asthmatic were lower than that in control (0.312±0.07 vs 0.607±0.2, p<0.05 and 0.445±0.13 vs 0.32±0.04, p<0.05, respectively). Total FoxP₃⁺CD₄⁺ cell and CD₄₅RA⁺Foxp₃^lo were higher in asthmatic (8.3%±1.3% vs 6.05%±1.8%, p=0.007 and 4.60%±1.04% vs 3.27%±1.03%, p=0.011, respectively). CD₄₅RA^-Foxp₃^hi was lower (0.75%±0.13% vs 0.93%±0.26%, p=0.021). After treatment, CD₄₅RA^-Foxp₃^hi was increased in MT compared to placebo group (1.16%±0.24% vs 0.89%±0.22%, p=0.01). TGF-β₁ levels had no correlation with those levels of pulmonary function.

Conclusion: The expression of TGF-β₁ was low in asthmatic children. Insufficient secretion of TGF-β₁ and the defection in activating FoxP₃⁺CD₄⁺ Treg cells might play an important role in pathogenesis of asthma. Up-regulation of expression of TGF-β₁ and induction of expression of CD₄₅RA^-Foxp₃^hi in Foxp₃⁺CD₄⁺Treg cells by MT may be one of the mechanisms by which airway inflammation is inhibited in asthma.