TY - JOUR
T1 - Role of interleukin-6 in cardiac inflammation and dysfunction after burn complicated by sepsis
AU - Zhang, Hongchao
AU - Wang, Huan You
AU - Bassel-Duby, Rhonda
AU - Maass, David L.
AU - Johnston, William E.
AU - Horton, Jureta W.
AU - Tao, Weike
PY - 2007/5
Y1 - 2007/5
N2 - 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)-α were measured. Cardiomyocyte intracellular calcium ([Ca2+]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-α, [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.
AB - 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)-α were measured. Cardiomyocyte intracellular calcium ([Ca2+]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-α, [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.
KW - Apoptosis
KW - Cardiac contractile function
KW - Fibrosis
KW - Tumor necrosis factor-α
KW - α-myosin heavy chain
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U2 - 10.1152/ajpheart.01150.2006
DO - 10.1152/ajpheart.01150.2006
M3 - Article
C2 - 17220181
AN - SCOPUS:34250896719
SN - 0363-6135
VL - 292
SP - H2408-H2416
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -