白细胞介素15在小鼠支气管哮喘发病中的作用

目的：通过检测哮喘小鼠血清、肺组织中白细胞介素15（IL-15）的表达，以及与IgE、IL-4、IFN-γ、肺泡灌洗液（BALF）中嗜酸粒细胞（EOS）的关系，探讨IL-15在小鼠支气管哮喘发病中的作用。方法：30只健康雌性BALB　C小鼠按完全随机设计原则分为OVA致敏并激发的哮喘模型组（A 组），OVA致敏、激发并予激素治疗组（B组）及正常对照组（C 组）共3组，每组10只。ELISA法检测血清IgE、IL-4、IFN-γ和IL-15的含量；收集BALF行Eos计数；HE染色观察气道炎症及半定量评定炎性细胞浸润程度；免疫组织化学法检测各组小鼠肺组织中IL-15的含量。结果：① 哮喘组小鼠发生行为学改变，肺部组织病理学可观察到明显的 EOS 浸润为主的炎症反应，BALF 中 EOS、血清IgE 和IL-4水平较对照组显著增高（P<0.01），而血清IFN-γ水平较对照组降低（P<0.01），以及IL-4／IFN-γ二者呈负相关关系(r=－0.859，P<0.01)，以上均显示哮喘模型制备成功。② 哮喘组小鼠血清IL-15 水平［（77.97±2.75）ng·L^-1］高于对照组［（34.63±1.44）ng·L^-1］（P<0.01）；血清IL-15水平与 IgE和IL-4水平均呈正相关关系(r= 0.681，r＝0.738，P<0.01)，与 IFN-γ 无相关性。③ 哮喘组小鼠肺组织中IL-15的含量高于对照组（P<0.01）；哮喘组肺组织中IL-15含量与BALF中EOS呈正相关关系(r= 0.787，P<0.01 )。④ 激素治疗组小鼠肺组织炎症明显减轻、BALF 中的 EOS计数减少、血清IgE水平下降、血清IL-15 的水平及肺组织中IL-15的含量均低于哮喘组（P<0.01）。结论：IL-15在哮喘中可能参与了Th2 类细胞因子IL-4的调节，对于Th1 类细胞因子IFN-γ无明显调节作用。IL-15可能参与了血清IgE水平的调节。IL-15还可能与哮喘 Eos增多有关，进而参与哮喘气道的慢性炎症。糖皮质激素可有效控制哮喘气道炎症。

Effect of interleukin-15 in pathogenesis of mouse bronchial asthma

Objective To measure the level of interleukin-15(IL-15) in serum and its expression in lung tissues,and analyze the correlations between IL-15 and IL-4,IFN-γ,eosinophil(Eos),and explore the effect of IL-15 on bronchial asthma.Methods Thirty femal BALB/C mice were randomly divided into three group(n=10),group A(asthma model),group B(corticosteroid treatment) and group C(normal control).All mice were killed 24 h after final OVA challenge.Blood were obtained for measurement of serum IgE,IL-4,IFN-γ and IL-15 levels by enzyme-linked immunoabsorbent assay(ELISA).Bronchoalveolar lavage fluid(BLAF) was collected for Eos count.The left lungs were isolated for pathological examination.The lung sections were stained with hematoxylin and eosin(HE).The expressions of IL-15 in lung tissues were measured by immunohistochemical SP method.Results ①The mouse asthma model appeared ethological changes specific to asthma,the Eos count in BALF was increased,and IgE and IL-4 levels in serum were also increased compared with control group(P<0.01).The lung tissues also appeared typical pathological changes and the inflammation cell score elevated.The level of serum IFN-γ was decreased(P<0.01).Correlation analysis showed negative relationship between IL-4 and IFN-γ(r=-0.859,P<0.01),there existed Th1/Th2 imbalance.② The level of serum IL-15 in group A(77.97 ng·L-1±2.75 ng·L-1) was higher than that in group C(34.63 ng·L-1±1.44 ng·L-1)(P<0.01).There were positive correlations between the serum IL-15 and IgE,IL-4 levels(r= 0.681,P<0.01;r= 0.738,P<0.01),while the serum IL-15 level had no correlation with IFN-γ.③ The expression of IL-15 in lung tissues in group A was higher than that in group C(P<0.01).There was a positive correlation between the expression of IL-15 in lung tissues and the Eos count in BALF(r= 0.787,P<0.01).④ In mice treated with inhaled budesonide(group B),the Eos count in BALF,the level of serum IgE,the level of serum IL-15 and the expression of IL-15 in lung tissues were lower than those in group A(all P<0.01).Conclusion IL-15 might contribute to promoting Th2 cells to secret cytokine IL-4,while not contribute to promoting Th1 cells to secret cytokine IFN-γ.IL-15 might be involved in the elevation of Eos and IgE,which suggests that IL-15 might be involved in the chronic inflammation of bronchial asthma.The inflammation of bronchial asthma could be inhibited by inhaled glucocorticoid.