Mechanism Of IFN-γ Inhibit Airway Inflammation And Airway Hypperresponsivness After RSV Reinfection

PART I ESTABLISHMENT AND IMPORTANCE OF THE MODEL OF RSV REINFECTION AT WEANING PERIODObjective:The present study was performed to investigate the immune response characteristics of mice primary infected at weaning period after reinfection by respiratory syncytial virus and its type of airway inflammation.Methods:Female C57BL/6 mice at the age of 3 weeks, were randomly divided into PBS control group, Adult primary infection group, Reinfection group. The mice’s weight were detected after primary infection or reinfection; Three and Seven days later, The mice were then killed to the number of cells in bronchoalevolar lavage fluid (BALF), inflammation in lung tissue and its score; The concentrations of IFN-y, IL-4,IL-5 and IL-17A in BALF were detected by ELISA.Results:the mice’s weight significantly decreased after RSV infection. Seven days after infection, the weight of Reinfection group were significantly lower than that of Adult primary infection group; the number of total cell, eosinophil, neutrophil, lymphocyte and macrophage of Reinfection group were remarkably higher than that of PBS control group and Adult primary infection group. The score of inflammation in lung tissue of Adult primary infection group and Reinfection group were remarkably higher than that of PBS control group. Moreover, The score of inflammation in lung tissue of Reinfection group were significantly higher than that of Adult primary infection group. The level of IFN-y was markedly higher in Adult primary infection group in contrast to other groups, while there were no differences of IL-4, IL-5 and IL-17A between Adult primary infection group and PBS control group. However, The level of IL-4, IL-5 and IL-17A were markedly higher in Reinfection group than that of other groups, meanwhile there were no differences of IFN-y in contrast to PBS control group.Conclusion:RSV reinfection aggravated the state of illness. The number of eosinophil and neutrophil in BALF and the concentrations of IL-4, IL-5 and IL-17A in Reinfection group significantly increased, it is similar to the Inflammation of asthma. Overall, RSV reinfection induced the development of asthma.PART II MECHANISM OF IFN-r INHIBIT AIRWAY INFLAMMATION AND AIRWAY HYPPERRESPONSIVNESS AFTER RSV REINFECTIONObjective:Compared the difference on airway inflammation and airway hyperresponsiveness between wild-type and IFN-y knockout mice after RSV reinfection. Study the mechanism of IFN-y on airway inflammation and airway hypperresponsivness after RSV reinfectionMethods:Female wild-type and IFN-y knockout mice at the age of 3 weeks, were randomly divided into PBS control group, Reinfection group. The mice’s weight were detected after primary infection or reinfection; Three and Seven days later, The mice were then killed to the number of cells in bronchoalevolar lavage fluid (BALF), inflammation in lung tissue and its score; The concentrations of IL-4, IL-5, IL-13 and IL-17A in BALF were detected by ELISA.Results:the mice’s weight significantly decreased after RSV infection. But the weight of wild-type and IFN-y knockout mice show no significant. Seven days after infection, Only Reinfection group of knockout mice were detected AHR. Reinfection group of knockout mice had significantly greater AHR than other groups. Three and seven days after infection, The number of total cell, eosinophil, neutrophil, lymphocyte of wild-type and IFN-γ knockout mice’s Reinfection group were remarkably higher than that of PBS control group. Moreover, The number of total cell, eosinophil, neutrophil, lymphocyte of IFN-γ knockout mice’s Reinfection group were remarkably higher than that of wild-type Reinfection group. The score of inflammation in lung tissue of wild-type and IFN-γ knockout mice’s Reinfection group were remarkably higher than that of PBS control group. Moreover, The score of inflammation in lung tissue of IFN-γ knockout mice’s Reinfection group were significantly higher than that of wild-type Reinfection group. Three days after infection, The level of IL-4, IL-17A were markedly higher in wild-type Reinfection group in contrast to PBS control group. The level of IL-4, IL-13, IL-17A were markedly higher in IFN-y knockout mice’s Reinfection group in contrast to PBS control group. Seven days after infection, The level of IL-4, IL-5, IL-17A were markedly higher in wild-type Reinfection group in contrast to PBS control group. The level of IL-4, IL-5, IL-13, IL-17A were markedly higher in IFN-γ knockout mice’s Reinfection group in contrast to PBS control group. Meanwhile, the level of IL-5 was-significantly increased in IFN-γ knockout mice’s Reinfection group compared to wild-type Reinfection group.Conclusions:IFN-γ can prevent the enhancement of AHR and mitigate the development of airway Inflammation. Its protective mechanism may inhibit the level of IL-5 and IL-13 in BALF, thereby reducing the Th2 cytokines mediating AHR and airway inflammation.