Johnston Richard A, Schwartzman Igor N, Flynt Lesley, Shore Stephanie A
Bldg. 1, Rm. 1304A, Physiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115-6021, USA.
Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L390-7. doi: 10.1152/ajplung.00007.2004. Epub 2004 Oct 29.
This study sought to examine the role of interleukin-6 (IL-6) in ozone (O(3))-induced airway injury, inflammation, and hyperresponsiveness (AHR). Subacute (72 h) exposure to 0.3 ppm O(3) significantly elevated bronchoalveolar lavage fluid (BALF) protein, neutrophils, and soluble TNF receptors (sTNFR1 and sTNFR2) in wild-type C57BL/6 (IL-6(+/+)) mice; however, all four outcome indicators were significantly reduced in IL-6-deficient (IL-6(-/-)) compared with IL-6(+/+) mice. Acute O(3) exposure (2 ppm for 3 h) increased BALF protein, KC, macrophage inflammatory protein(MIP)-2, eotaxin, sTNFR1, and sTNFR2 in IL-6(+/+) mice. However, MIP-2 and sTNFR2 were not significantly increased following O(3) exposure in IL-6(-/-) mice. Increases in BALF neutrophils induced by O(3) (2 ppm for 3 h) were also significantly reduced in IL-6(-/-) vs. IL-6(+/+) mice. Airway responsiveness to methacholine was measured by whole body plethysmography before and following acute (3 h) or subacute (72 h) exposure to 0.3 ppm O(3). Acute O(3) exposure caused AHR in both groups of mice, but there was no genotype-related difference in the magnitude of O(3)-induced AHR. AHR was absent in mice of either genotype exposed for 72 h. Our results indicate that IL-6 deficiency reduces airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following acute high dose and/or subacute low-dose O(3) exposure, but has no effect on O(3)-induced AHR.
本研究旨在探讨白细胞介素-6（IL-6）在臭氧（O₃）诱导的气道损伤、炎症和高反应性（AHR）中的作用。野生型C57BL/6（IL-6（+/+））小鼠亚急性（72小时）暴露于0.3 ppm O₃后，支气管肺泡灌洗液（BALF）中的蛋白质、中性粒细胞以及可溶性肿瘤坏死因子受体（sTNFR1和sTNFR2）显著升高；然而，与IL-6（+/+）小鼠相比，IL-6缺陷型（IL-6（-/-））小鼠的所有这四项结果指标均显著降低。急性O₃暴露（2 ppm，持续3小时）使IL-6（+/+）小鼠的BALF蛋白质、KC、巨噬细胞炎性蛋白（MIP）-2、嗜酸性粒细胞趋化因子、sTNFR1和sTNFR2增加。然而，IL-6（-/-）小鼠在O₃暴露后MIP-2和sTNFR2没有显著增加。与IL-6（+/+）小鼠相比，IL-6（-/-）小鼠中由O₃（2 ppm，持续3小时）诱导的BALF中性粒细胞增加也显著减少。在急性（3小时）或亚急性（72小时）暴露于0.3 ppm O₃之前和之后，通过全身体积描记法测量对乙酰甲胆碱的气道反应性。急性O₃暴露在两组小鼠中均引起AHR，但在O₃诱导的AHR程度上没有基因型相关差异。暴露72小时的两种基因型小鼠均未出现AHR。我们的结果表明，IL-6缺陷可减轻急性高剂量和/或亚急性低剂量O₃暴露后的气道嗜中性粒细胞增多以及BALF中sTNFR1和sTNFR2的水平，但对O₃诱导的AHR没有影响。
