The effect of interleukin-18 on airway inflammation in asthmatic murine models and its mechanisms

Abstract

In order to investigate the effect of interleukin-18 (IL-18) on airway inflammation in asthmatic murine models and its mechanisms, BALB/C mice were randomly divided into three groups (n=10 in each group): group A (control group); group B (asthmatic model group); group C (IL-18-treated group). The asthmatic model was established in groups B and C by respiratory syncytial virus (RSV) killed by ultraviolet. Saline solution (0.1 mL) and IL-18 (0.1 mL, 1 μg) were intraperitoneally injected respectively in groups B and C at 7 time points (day 1, 2, 7, 8, 9, 21, 22). The number of eosinophils (EOS) and plasmacytes in the airway was observed. The levels of interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The results showed that symptoms of asthma in group C were more severe than in groups A and B. In group A, there were no EOS and plasmacytes in the airway submucosa. The number of EOS [15±3 (average cell counts per microscopic visual field, the same below)] and plasmacytes (10±2) in group B were increased significantly. However, the number of EOS and plasmacytes in group C (6±2 and 2±1, respectively) was decreased significantly as compared with group B (both P<0.05). The levels of IFN-γ in groups A, B and C were 31±3, 40±5 and 63±5 pg/mL respectively, and those in group C were significantly higher than in groups A and B (both P<0.05). It was suggested that the mechanism by which IL-18 inhibited the airway inflammation in asthmatic mice might be contributed to the fact that IL-18 could induce the induction of IFN-γ.

Keywords

interleukin-18 / asthma / eosinophil / plasmacyte / interferon gamma

References

[1] ZhouL. F., ZhuY., CuiX. F., et al.. Arsenic trioxide, a potent inhibitor of NF-kappaB, abrogates allergen-induced airway hyperresponsiveness and inflammation. Respir Res, 2006, 7: 146

[2] MengY., MaQ. Y., KouX. P., et al.. Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis. World J Gastroenterol, 2005, 11: 525-528

[3] HofstraC. L., ArkI. V., HofmanG., et al.. Prevention of Th₂ like cell responses by load ministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia and serum IgE levels. J Immunol, 1998, 161: 5054-5060

[4] GordonJ. R., LiF., NayyarA., et al.. CD8 alpha+, but not CD8 alpha-, dendritic cells tolerize Th2 responses via contact-dependent and-independent mechanisms, and reverse airway hyperresponsiveness, Th2, and eosinophil responses in a mouse model of asthma. J Immunol, 2005, 175: 1516-1522

[5] KaanH., Dimich-WardH., ManfredaJ., et al.. Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months. Ann Allergy Asthma Immunol, 2000, 84: 37-42

[6] KumanoK., NakaoA., NakajimaH., et al.. Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways. Am J Respir Crit Care Med, 1999, 160: 873-878

[7] ShinH. D., KimL. H., ParkB. L., et al.. Association of interleukin 18 polymorphisms with specific IgE levels to mite allergens among asthmatic patients. Allergy, 2005, 60: 900-906

[8] IshiharaC., OchiaiK., KagamiM., et al.. Human peripheral eosinophils express functional interferon-gamma receptors (IFN-gammaR). Clin Exp Immunol, 1997, 110: 524-529

[9] KoningH., NeijensH. J., BaertM. R., et al.. T cell subsets and cytokines in allergic and nonallergic children. Cytokine, 1997, 9: 416-426

[10] LagierB., LebelB., BousquetJ., et al.. Different modulation by histamine of IL-4 and interferon-gamma (IFN-gamma) release according to the phenotype of human Th0, Th1 and Th2 clones. Clin Exp Immunol, 1997, 108: 545-551

[11] CohnL., HerrickC., NiuN., et al.. IL-4 promotes airway eosinophilia by suppressing IFN-gamma production: defining a novel role for IFN-gamma in the regulation of allergic airway inflammation. J Immunol, 2001, 166: 2760-2767