Acute Lung Injury Induces Cardiovascular Dysfunction Effects of IL-6 and Budesonide/Formoterol

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

来源：American Journal of Respiratory Cell and Molecular Biology, 2011, 45(3): 510-516.

DOI：10.1165/rcmb.2010-0169OC

• inhaled corticosteroid
• long-acting beta 2 agonist
• systemic inflammation
• cardiovascular event

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 beta 2 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 5 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.

• 出版日期2011-9
• 单位河北医科大学