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

Koichi Suda, Masashi Tsuruta, Jihyoun Eom, Chris Or, Tammy Mui, Jen-Erh Jaw, Yuexin Li, Ni Bai, Joseph Kim, Julie Man, David Ngan, Jee Lee, Søren Hansen, Seung-Won Lee, Sheena Tam, S Paul Man, Stephan Van Eeden, Don D Sin

    Research output: Contribution to journalJournal articleResearchpeer-review

    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.

    Original languageEnglish
    JournalAmerican Journal of Respiratory Cell and Molecular Biology
    Volume45
    Issue number3
    Pages (from-to)510-516
    ISSN1044-1549
    DOIs
    Publication statusPublished - 2011

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