[The effect of montelukast on airway remodeling and the expression of interleukins and transforming growth factor-beta2 mRNA].
OBJECTIVE
To study the relation between Interleukin-4 (IL-4), IL-5, IL-13, transforming growth factor-beta(2) (TGF-beta(2)) and airway remodeling and to investigate the effects of Montelukast (MK) on airway inflammation and airway remodeling of asthma.


METHODS
Twenty female BALB/c mice were randomly divided into a remodeling group and a treatment group (MK group), with 10 BALB/c mice in each group. The mice were sensitized by ovalbumin (OVA), and only the MK group was treated with MK (15 mg/kg). The number of total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. Light and electronic microscope were used to detect the pathologic histology and morphologic change. In situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure IL-4, L-5, IL-13, and TGF-beta(2) mRNAs in the lung.


RESULTS
The numbers of total cells and eosinophils in BALF of the remodeling group were (5.4 +/- 1.1) x 10(5)/ml and 2.32 +/- 0.20, while those of the treatment group were (3.9 +/- 1.6) x 10(5)/ml and 1.64 +/- 0.32, respectively, the difference being significant (P < 0.01). Histological and electronic microscopic examination showed extensive airway inflammation, notably accumulation of significant numbers of eosinophils and lymphocytes in the remodeling group. Other features including prominent proliferation of airway epithelial cells protruded like fingers, increased thickness of smooth muscle, hyperplasia of connective tissue, goblet cell hyperplasia and a marked increase in airway mucus secretion with mucus plugging and extensive collagen deposition around the airways were also noted in the remodeling group. In the treatment group, the inflammation was significantly decreased, with decreased production of mucus, decreased collagen and granule of mucus around airway, less proliferation of airway epithelium, smooth muscle hypertrophy and airway spasm. In situ hybridization showed that the expression of IL-13 mRNA and TGF-beta(2) mRNA in the lung of the remodeling group were 24 +/- 7 and 17 +/- 5 respectively, while those of the treatment group were 17 +/- 4 and 10 +/- 3. RT-PCR results showed that the absorbance of IL-4 mRNA and IL-5 mRNA in the lung of the remodeling group were 0.91 and 0.96, while those of the treatment group were 0.22 and 0.35; the differences between the groups were all significant (all P < 0.01).


CONCLUSIONS
MK could effectively inhibit airway remodeling, which suggests a possible role of cysteinyl leukotrienes in the pathogenesis of chronic allergic inflammation with fibrosis.
Bai
Jian-wen
JW
Department of Respiratory Medicine, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Deng
Wei-wu
WW
Wu
Hua-cheng
HC
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D003521:Cyclopropanes; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D013440:Sulfides; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053781:Transforming Growth Factor beta2
D000085:Acetates; D003521:Cyclopropanes; D007378:Interleukins; D020024:Leukotriene Antagonists; D011804:Quinolines; D012333:RNA, Messenger; D013440:Sulfides; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C093875:montelukast