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.

Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs

“…Consistent with published results (91,93), we found that burn caused significant inflammatory infiltration and disorganization of cardiomyocytes (Fig. 10B).…”

Left ventricular global longitudinal strain is independently associated with mortality in septic shock patients

“…Various factors contribute to the deteriorated LV function, such as inflammation, free radicals, toxins, and mitochondrial dysfunction [20][21][22][23][24]. Increasing evidence validates the correlation between myocardial dysfunction and high mortality rates [25][26][27].…”

Effects of Blood Purification on Serum Levels of Inflammatory Cytokines and Cardiac Function in a Rat Model of Sepsis

“…However, in the results of our study, it showed that, compared with the normal control group and the sham operation group, the serum level of TNF-α in the model group and the sham BP treatment group had significantly increased, while compared with the model group and the sham BP treatment group, the serum level of TNF-α in the BP treatment group had significantly decreased. The uncommon effect they observed with TNF-α could be explained by that the level of TNF-α was negatively correlated with cardiac function in the occurrence of sepsis [26]. As the main anti-inflammatory cytokine, IL-10 functions at immune suppression and plays an anti-inflammatory role [27].…”