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.
Johnston
Richard A
RA
Bldg. 1, Rm. 1304A, Physiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115-6021, USA. rajohnst@hsph.harvard.edu
Schwartzman
Igor N
IN
Flynt
Lesley
L
Shore
Stephanie A
SA
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004334:Drug Administration Schedule; D005260:Female; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
D015850:Interleukin-6; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D010126:Ozone