Particulate matter induces translocation of IL-6 from the lung to the systemic circulation

Takashi Kido, Eiji Tamagawa, Ni Bai, Koichi Suda, Huei Hsin C. Yang, Yuexin Li, Gary Chiang, Kazuhiro Yatera, Hiroshi Mukae, Don D. Sin, Stephan F. Van Eeden

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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(PM10). C57BL/6 mice were intratracheally exposed to a single instillation of PM10 (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 toPM10. At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM10 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 PM10. In IL-6 knockout mice, the instillation of recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM10 did not cause vascular dysfunction. These results support our hypothesis that exposure to PM10 increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number2
DOIs
Publication statusPublished - 01-02-2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Kido, T., Tamagawa, E., Bai, N., Suda, K., Yang, H. H. C., Li, Y., Chiang, G., Yatera, K., Mukae, H., Sin, D. D., & Van Eeden, S. F. (2011). Particulate matter induces translocation of IL-6 from the lung to the systemic circulation. American Journal of Respiratory Cell and Molecular Biology, 44(2), 197-204. https://doi.org/10.1165/rcmb.2009-0427OC