IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis

• Published in: iScience 2023-09, Vol.26 (9), p.107544-107544, Article 107544
• Main Authors: Zhao, Mengmeng, Zheng, Zihui, Zhang, Pingan, Xu, Yao, Zhang, Jishou, Peng, Shanshan, Liu, Jianfang, Pan, Wei, Yin, Zheng, Xu, Shuwan, Wei, Cheng, Wan, Jun, Wang, Menglong
• Format: Article
• Language: English
• Subjects: Cell biology; Immune response; Immunology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107544

Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis. [Display omitted] •IL-30 KO aggravates sepsis-induced cardiac dysfunction•IL-30 KO promotes LPS-induced Ly6Chigh macrophage polarization and pyroptosis•The level of IL-30 is increased in sepsis patients and associated with the prognosis Molecular biology; Immunology; Immune response; Cell biology