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IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization
Mengmeng Zhao1,2,3, Zihui Zheng1,2,3, Pingan Zhang4
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.
Abstract:
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.
Insights
Interleukin-30 (IL-30) protects against sepsis-induced myocardial dysfunction by reducing inflammation. IL-30 inhibits pro-inflammatory macrophage polarization and pyroptosis, improving cardiac function during sepsis.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Sepsis-induced myocardial dysfunction (SIMD) is a severe complication impacting patient outcomes.
- The role of Interleukin-30 (IL-30) in SIMD is not well understood.
- IL-30 is known for its anti-inflammatory properties in other conditions.
Purpose of the Study:
- To investigate the protective effects of IL-30 in a mouse model of SIMD.
- To elucidate the underlying mechanisms of IL-30's action in the heart during sepsis.
Main Methods:
- Cecum ligation and puncture (CLP) model in mice to induce sepsis.
- Analysis of IL-30 expression in cardiac tissue.
- Investigated effects of IL-30 deficiency, neutralization, and recombinant IL-30 administration.
- Assessed macrophage polarization and pyroptosis, including NLRP3 inflammasome involvement.
Main Results:
- IL-30 expression was upregulated in cardiac tissue during sepsis, primarily from macrophages.
- IL-30 deficiency worsened cardiac dysfunction and injury post-CLP.
- Recombinant IL-30 treatment improved cardiac function and reduced injury.
- IL-30 deficiency promoted pro-inflammatory macrophage polarization and pyroptosis, which was reversed by NLRP3 inhibition.
- Recombinant IL-30 suppressed pro-inflammatory macrophage polarization and pyroptosis.
Conclusions:
- IL-30 plays a crucial protective role in mitigating sepsis-induced myocardial dysfunction.
- IL-30 exerts its protective effects by inhibiting pro-inflammatory macrophage polarization and pyroptosis.
- Targeting IL-30 may represent a therapeutic strategy for SIMD.
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