IL-13 and IFN-γ:: Interactions in lung inflammation
IL-13 and IFN-γ:: Interactions in lung inflammation
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DOI：
10.4049/jimmunol.167.3.1769
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Grünig, G
中科院分区：
文献类型：
--
作者：
Ford, JG;Rennick, D;Grünig, G
肺部的慢性炎症性疾病，如哮喘，常常与混合的（Th2和Th1）T细胞反应相关。我们研究了关键的Th1和Th2细胞因子，即干扰素 -γ和白细胞介素 - 13，对肺部反应的影响。在由混合T细胞反应诱导的气道炎症小鼠模型中，发现Th1（干扰素 -γ阳性）细胞的数量与气道高反应性呈负相关。在这些小鼠中，白细胞介素 - 13阻断部分抑制了气道高反应性和杯状细胞增生，但不抑制炎症。相反，在对相同抗原产生极化Th2反应的小鼠中，白细胞介素 - 13阻断抑制了气道高反应性、杯状细胞增生和气道炎症。这些结果表明干扰素 -γ的存在会调节白细胞介素 - 13在肺部的作用。为了验证这一假设，给野生型小鼠鼻内给予重组细胞因子。干扰素 -γ抑制了白细胞介素 - 13诱导的杯状细胞增生和气道嗜酸性粒细胞增多。同时，干扰素 -γ和白细胞介素 - 13增强了彼此的作用。在给予白细胞介素 - 13和干扰素 -γ的小鼠气道中，白细胞介素 - 6水平升高，自然杀伤细胞以及表达MHC II类和高水平CD86的CD11c阳性细胞数量也增加。总之，干扰素 -γ对白细胞介素 - 13诱导的肺部变化具有双面效应（抑制一些，增强另一些）。这可能是Th1反应在Th2反应诱导的肺损伤中作用不明确的原因。
Chronic inflammatory diseases of the lungs, such as asthma, are frequently associated with mixed (Th2 and Th1) T cell responses. We examined the impact of critical Th1 and Th2 cytokines, IFN-gamma and IL-13, on the responses in the lungs. In a mouse model of airway inflammation induced by mixed T cell responses, the number of Th1 (IFN-gamma -positive) cells was found to be negatively correlated with airway hyperreactivity. In these mice, blockade of IL-13 partially inhibited airway hyperreactivity and goblet cell hyperplasia but not inflammation. In contrast, in mice that responded with a polarized Th2 response to the same Ag, blockade of IL-13 inhibited airway hyperreactivity, goblet cell hyperplasia, and airway inflammation. These results indicated that the presence of IFN-gamma would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-gamma inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-gamma and IL-13 potentiated each other's effects. In the airways of mice given IL-13 and IFN-gamma, levels of IL-6 were increased as well as numbers of NK cells and of CD11c-positive cells expressing MHC class II and high levels of CD86. In conclusion, IFN-gamma has double-sided effects (inhibiting some, potentiating others) on IL-13-induced changes in the lungs. This may be the reason for the ambiguous role of Th1 responses on Th2 response-induced lung injury.