Age-Dependent Differences of Interleukin-6 Activity in Cardiac Function after Burn Complicated by Sepsis 1

Interleukin (IL)-6 is a pleiotropic cytokine that is activated after acute injuries, and plays an important role during aging. We aim to define the role of IL-6 on myocardial dysfunction following a 40% total body surface area burn followed by late (7 days) S. pneumoniae sepsis (burn plus sepsis) in 2and 14-month-old wild type and IL-6−/− mice. We measured global hemodynamic and cardiac contractile function with left ventricular pressure-volume analysis 24 hours after sepsis induction, and measured phophorylated signal transducer and activator of transcription 3 (p-STAT-3), tumor necrosis factor (TNF)-α, and IL-1β in the heart with Western blot analysis. We also measured mRNA expression of IL-6, TNF-α, and IL-1β. Sham injured mice did not manifest any appreciable level of p-STAT-3 or functional deficiencies regardless of age or presence of the IL-6 gene. Burn plus sepsis injury was associated with a significant deterioration of global hemodynamic and cardiac contractile function in WT mice in both age groups. This dysfunction was attenuated by IL-6 deficiency at age 2 months, but accentuated at age 14 months. Aging was associated with an increase in mRNA expression of IL-6 (WT mice), TNF-α, and IL-1β (all mice). At age 14 months, IL-6 deficient mice exhibited a greater TNF-α mRNA expression than the wild type mice. We conclude aging is associated with altered cytokine gene transcription, and burn plus sepsis injury further intensifies such gene responses. IL-6 deficiency does not abrogate STAT-3 phosphorylation and it may enhance expression of other inflammatory cytokines. The differential effects of IL-6 deficiency on the cardiac function in young and aging mice cannot be explained by cytokine gene expression alone, and require further studies. 1This work is supported by the National Institute of General Medical Sciences 1K08GM073141 (W.T.) and 5P50GM21681-41 (J.W.H. and J.A.T.). This work was presented at the 31st Annual Conference on Shock, June 28 – July 2, 2008, Cologne, Germany. This paper is in loving memory of Jureta W. Horton, our inspirational mentor, supporter, and dear friend. Address Correspondence Requests to: Weike Tao, Department of Anesthesiology and Pain Management, the University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9068. Phone: 214-648-4840; Fax: 214-648-2229; email: weike.tao@utsouthwestern.edu. Conflict of Interest Statement There is no conflict of interest in the paper “Age-Dependent Differences of Interleukin-6 Activity in Cardiac Function after Burn Complicated by Sepsis” for consideration of publication in Burns. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Burns. Author manuscript; available in PMC 2011 March 1. Published in final edited form as: Burns. 2010 March ; 36(2): 232–238. doi:10.1016/j.burns. 2009.02. 019. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript