title: Particulate matter induces translocation of IL-6 from the lung to the systemic circulation.
abstract: The biological mechanisms responsible for an association between elevated concentrations of ambient particulate matter (PM) and increased cardiovascular morbidity and mortality remain unclear. Our laboratory showed that exposure to PM induces systemic inflammation that contributes to vascular dysfunction. This study was designed to determine whether the lung is a major source of systemic inflammatory mediators, using IL-6 as a surrogate marker. We also sought to determine the impact on vascular dysfunction after exposure to PM of less than 10 μm in diameter (PM(10)). C57BL/6 mice were intratracheally exposed to a single instillation of PM(10) (10 or 200 μg) or saline. Four hours or 24 hours after exposure, venous and arterial blood samples were simultaneously collected from the right atrium and descending aorta. Concentrations of IL-6 were measured in bronchoalveolar lavage fluid (BALF) and serum samples. Vascular functional responses to acetylcholine (ACh) and phenylephrine were measured in the abdominal aorta. Concentrations of IL-6 in BALF samples were increased at 4 and 24 hours after exposure to PM(10). At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM(10) reversed this arteriovenous gradient, 4 hours after exposure. The relaxation responses of the abdominal aorta to ACh decreased 4 hours after exposure to 200 μg PM(10). In IL-6 knockout mice, the instillation of recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM(10) did not cause vascular dysfunction. These results support our hypothesis that exposure to PM(10) increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.
authors.affiliation: James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kido
authors.forename: Eiji
authors.initials: E
authors.lastname: Tamagawa
authors.forename: Ni
authors.initials: N
authors.lastname: Bai
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.forename: Huei-Hsin C
authors.initials: HH
authors.lastname: Yang
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Li
authors.forename: Gary
authors.initials: G
authors.lastname: Chiang
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: Stephan F
authors.initials: SF
authors.lastname: Van Eeden
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000503:physiopathology; D001693:Biological Transport, Active; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D052638:Particulate Matter