Role of interleukin-6 in murine airway responses to ozone

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.