title: Role of interleukin-6 in cardiac inflammation and dysfunction after burn complicated by sepsis.
abstract: To examine the role of myocardial interleukin-6 (IL-6) in myocardial inflammation and dysfunction after burn complicated by sepsis, we performed 40% total body surface area contact burn followed by late (7 days) Streptococcus pneumoniae pneumonia sepsis in wild-type (WT) mice, IL-6 knockout (IL-6 KO) mice, and transgenic mice overexpressing IL-6 in the myocardium (TG). Twenty-four hours after sepsis was induced, isolated cardiomyocytes were harvested and cultured in vitro, and supernatant concentrations of IL-6 and tumor necrosis factor (TNF)-alpha were measured. Cardiomyocyte intracellular calcium ([Ca(2+)](i)) and sodium ([Na(+)](i)) concentrations were also determined. Separate mice in each group underwent in vivo global hemodynamic and cardiac function assessment by cannulation of the carotid artery and insertion of a left ventricular pressure volume conductance catheter. Hearts from these mice were collected for histopathological assessment of inflammatory response, fibrosis, and apoptosis. In the WT group, there was an increase in cardiomyocyte TNF-alpha, [Ca(2+)](i), and [Na(+)](i) after burn plus sepsis, along with cardiac contractile dysfunction, inflammation, and apoptosis. These changes were attenuated in the IL-6 KO group but accentuated in the TG group. We conclude myocardial IL-6 mediates cardiac inflammation and contractile dysfunction after burn plus sepsis.
authors.affiliation: Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines, Dallas, TX 75390-9068, USA.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhang
authors.forename: Huan-You
authors.initials: HY
authors.lastname: Wang
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: David L
authors.initials: DL
authors.lastname: Maass
authors.forename: William E
authors.initials: WE
authors.lastname: Johnston
authors.forename: Jureta W
authors.initials: JW
authors.lastname: Horton
authors.forename: Weike
authors.initials: W
authors.lastname: Tao
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009205:Myocarditis / Q000150:complications / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000150:complications / Q000276:immunology*; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D015850:Interleukin-6