[The effect of gamma interferon gene transfer on airway inflammation in asthmatic mice].

Objective: To study the effect of airway gamma interferon (IFN-gamma) plasmid gene transfer on airway inflammation in asthmatic mice.

Methods: Forty C57BL/6 mice were randomly divided into four groups: a control group (group A), an asthmatic group (group B), a plasmid group (group C) and an IFN-gamma plasmid group (group D), 10 mice in each group. Except group A, other groups were sensitized with 0.1 ml 0.1% ovalbumin (OVA) by a combination of intraperitoneal injection and repeated 50 microl 1% OVA intranasal challenges to establish the mouse asthma model. In group A, normal saline of the equal volume was given instead of 0.1% OVA 0.1 ml and 1% OVA 50 microl. Group C was intranasally administered 50 microl mixture of plasmid pcDNA3.1(-) and Lipofectamine 2000, while 50 microl mixture of IFN-gamma plasmid and Lipofectamine 2000 was administered for the mice of group D. Bronchoalveolar lavage fluid (BALF) cell count and differential were studied. Interleukin-4 (IL-4), interleukin-5 (IL-5) and IFN-gamma in BALF were determined. Pathologic changes in lung tissues were observed.

Results: The differences were significant (P < 0.05) when the numbers of inflammation cells, eosinophils, neutrophils and lymphocytes in BALF of group B [(0.102 +/- 0.020) x 10(9)/L, (0.0193 +/- 0.0047) x 10(9)/L, (0.0107 +/- 0.0039) x 10(9)/L, (0.0255 +/- 0.0042) x 10(9)/L, respectively] were compared with those of group A [(0.082 +/- 0.012) x 10(9)/L, (0.0041 +/- 0.0009) x 10(9)/L, (0.0051 +/- 0.0016) x 10(9)/L, (0.0201 +/- 0.0019) x 10(9)/L, respectively]. The numbers of inflammation cells, eosinophils, neutrophils and lymphocytes in BALF of group D [(0.086 +/- 0.016) x 10(9)/L, (0.0116 +/- 0.0031) x 10(9)/L, (0.0062 +/- 0.0018) x 10(9)/L, (0.0182 +/- 0.0041) x 10(9)/L, respectively] were also significantly different (P < 0.05) as compared with those of group B. The IL-4, IL-5 and IFN-gamma levels in BALF of group B [(39.2 +/- 5.1) pg/ml, (83.7 +/- 4.7) pg/ml, (15.7 +/- 2.7) pg/ml, respectively] were significantly different (P < 0.05) as compared with those of group A [(13.3 +/- 1.9) pg/ml, (12.1 +/- 2.3) pg/ml, (31.8 +/- 7.9) pg/ml, respectively]. The IL-4, IL-5 and IFN-gamma levels of group D [(16.4 +/- 3.2) pg/ml, (26.3 +/- 3.4) pg/ml, (65.4 +/- 10.4) pg/ml] were also different (P < 0.05) from those of group B. Lung inflammation was examined in HE stained sections. There was no obvious infiltration of inflammatory cells in the airways of group A. However, there were a great number of inflammatory cells in the interstitial and peribronchovascular regions of group B and group C. Group D exhibited reduced epithelial damage and less infiltration of mononuclear cells and polymorphs in the interstitial and peribronchovascular regions, as compared with group B or group C.

Conclusions: These findings suggest that transtracheal IFN-gamma gene transfer is effective in modulating the imbalance of Th1/Th2 in BALF and inhibiting airway inflammation of asthmatic mice. The result provides experimental data for developing a novel therapeutic approach to asthma.