Modulation of myocardial injury in polymicrobial sepsis: The dual role of interleukin-13 in cardiac inflammation and stress.

Abstract

Polymicrobial sepsis is associated with a poor prognosis due to severe type-1 innate inflammation triggered by immune cells, such as dendritic cells and macrophages. This immune response frequently leads to damage in the heart. Although interleukin (IL)-13 is thought to play a protective role in organ inflammation, its function in polymicrobial sepsis remains unclear. We aimed to investigate the role of IL-13 in modulating myocardial injury during cecal ligation and puncture (CLP)-induced sepsis using a murine model. Cardiac troponin I (cTnI), a biomarker for myocardial damage, was measured in both IL-13-deficient (KO) and wild type (WT) mice subjected to CLP. Contrary to the conventional view of IL-13 as a protective cytokine, IL-13-competent mice exhibited significantly higher serum cTnI levels than IL-13-deficient mice, indicating exacerbated myocardial injury. Elevated cardiac tumor necrosis factor-alpha (TNF-α) levels and IL-1β in WT CLP mice corroborated this finding, suggesting IL-13's role in enhancing the inflammatory response. In vitro assays with bone marrow-derived dendritic cells (BMDCs) stimulated with lipopolysaccharide and Group A Streptococcus revealed a dose-dependent suppression of TNF-α and IL-6 production by recombinant IL-13. These findings indicate a complex role of IL-13 in sepsis, modulating inflammation but potentially increasing myocardial stress.