Bruselle G G, Kips J C, Peleman R A, Joos G F, Devos R R, Tavernier J H, Pauwels R A
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Am J Respir Cell Mol Biol. 1997 Dec;17(6):767-71. doi: 10.1165/ajrcmb.17.6.2820.
T-helper 2 (Th2)-like cells are thought to play a crucial role in the pathogenesis of the eosinophilic airway inflammation observed in asthma. In a murine model of allergen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), we have shown that interleukin (IL)-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE. In the present study, we investigated the role of interferon-gamma (IFN-gamma) in the inhibitory effects of IL-12 on allergic airway inflammation. Repeated daily exposure of actively immunized mice to aerosolized ovalbumin (OVA), as compared with aerosolized saline (SAL), induced a significant increase in bronchoalveolar lavage fluid (BALF) eosinophilia and OVA-specific serum IgE in both IFN-gamma-receptor-deficient (IFN-gammaR KO) and wild-type mice. As compared with placebo (PLAC), administration of recombinant murine IL-12 (rmIL-12) during the daily aerosol exposure (but not at the time of immunization) significantly inhibited BALF eosinophilia in both IFN-gammaR KO mice and wild-type controls, without influencing the production of specific IgE. In contrast, administration of rmIL-12 during the active immunization inhibited both BALF eosinophilia and specific IgE in wild-type mice as compared with littermates given PLAC; however, treatment with rmIL-12 during immunization, in comparison with PLAC, caused a significant increase in BALF eosinophilia and specific IgE in IFN-gammaR KO mice. These results demonstrate that inhibition of the allergen-induced eosinophil influx in murine airways by IL-12 is IFN-gamma-dependent during the initial sensitization, but becomes IFN-gamma-independent during the secondary response.
辅助性T细胞2（Th2）样细胞被认为在哮喘中观察到的嗜酸性气道炎症的发病机制中起关键作用。在变应原诱导的气道嗜酸性粒细胞增多和支气管高反应性（BHR）的小鼠模型中，我们已经表明，尽管存在循环特异性IgE，但白细胞介素（IL）-12可以抑制抗原诱导的气道变化。在本研究中，我们研究了干扰素-γ（IFN-γ）在IL-12对过敏性气道炎症的抑制作用中的作用。与雾化生理盐水（SAL）相比，将主动免疫的小鼠每天重复暴露于雾化卵清蛋白（OVA），在干扰素-γ受体缺陷（IFN-γR KO）小鼠和野生型小鼠中均诱导支气管肺泡灌洗液（BALF）嗜酸性粒细胞增多和OVA特异性血清IgE显著增加。与安慰剂（PLAC）相比，在每天雾化暴露期间（但不是在免疫时）给予重组小鼠IL-12（rmIL-12）可显著抑制IFN-γR KO小鼠和野生型对照中的BALF嗜酸性粒细胞增多，而不影响特异性IgE的产生。相反，与给予PLAC的同窝小鼠相比，在主动免疫期间给予rmIL-12可抑制野生型小鼠中的BALF嗜酸性粒细胞增多和特异性IgE；然而，与PLAC相比，在免疫期间用rmIL-12治疗导致IFN-γR KO小鼠中的BALF嗜酸性粒细胞增多和特异性IgE显著增加。这些结果表明，IL-12对小鼠气道中变应原诱导的嗜酸性粒细胞流入的抑制在初始致敏期间是IFN-γ依赖性的，但在二次反应期间变为IFN-γ非依赖性的。
