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, Srøen Hansen, Seung Won Lee, Sheena Tam, S. Paul Man, Stephan Van Eeden, Don D. Sin

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

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 b2 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 whetherbudesonide/formoterol ameliorates this process. Wild-type mice were pretreated for 3 hours with intratracheal budesonide, formoterol, or both, before LPS wassprayed 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
Pages (from-to)510-516
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number3
DOIs
Publication statusPublished - 2011 Sep 1

Keywords

  • Cardiovascular event
  • Inhaled corticosteroid
  • Long-acting β2 agonist
  • Systemic inflammation

ASJC Scopus subject areas

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

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