Acute lung injury induces cardiovascular dysfunction: effects of IL-6 and budesonide/formoterol.

TitleAcute lung injury induces cardiovascular dysfunction: effects of IL-6 and budesonide/formoterol.
Publication TypeJournal Article
Year of Publication2011
AuthorsSuda, K, Tsuruta, M, Eom, J, Or, C, Mui, T, Jaw, J-E, Li, Y, Bai, N, Kim, J, Man, J, Ngan, D, Lee, J, Hansen, S, Lee, S-W, Tam, S, S Man, P, Van Eeden, S, Sin, DD
JournalAm J Respir Cell Mol Biol
Volume45
Issue3
Pagination510-6
Date Published2011 Sep
ISSN1535-4989
KeywordsAcetylcholine, Acute Lung Injury, Adrenal Cortex Hormones, Animals, Bronchoalveolar Lavage Fluid, Bronchodilator Agents, Budesonide, Cardiovascular Diseases, Ethanolamines, Inflammation, Interleukin-6, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Vasodilation
Abstract

Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were pretreated for 3 hours with intratracheal budesonide, formoterol, or both, before LPS was sprayed into their tracheas. IL-6-deficient mice were similarly exposed to LPS. Four hours later, bronchoalveolar lavage fluid (BALF) and serum were collected, and endothelial and cardiac functions were measured, using wire myography of the aortic tissue and echocardiography, respectively. LPS significantly impaired vasodilatory responses to acetylcholine (P < 0.001) and cardiac output (P = 0.002) in wild-type but not IL-6-deficient mice. Intratracheal instillations of exogenous IL-6 into IL-6-deficient mice restored these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac output, P = 0.025). Pretreatment with the combination of budesonide and formoterol, but not either alone, ameliorated the vasodilatory responses to acetylcholine (P = 0.018) and cardiac output (P < 0.001). These drugs also attenuated the rise in the systemic expression of IL-6 (P < 0.05) related to LPS. IL-6 contributes to the cardiovascular dysfunction related to LPS, and pretreatment with budesonide/formoterol reduces the systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular events related to ALI.

DOI10.1165/rcmb.2010-0169OC
Alternate JournalAm. J. Respir. Cell Mol. Biol.
PubMed ID21169556
Grant List / / Canadian Institutes of Health Research / Canada