What is the clinical evidence from this study?

Study design: Other. Population: Lipopolysaccharide-induced cardiac injury. Intervention: MCTR1 vs. LPS alone. Primary outcome: Cardiac function (LVESV, FS, EF) and neutrophil infiltration.

April 26, 2021Open Access

γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

YYYi YangUniversity of the Cordilleras XLXinyu LiBeijing Tongren Hospital LLLin-Chao LiWenzhou Medical University

Key Result

MCTR1 significantly enhanced cardiac function and reduced neutrophil infiltration in LPS-induced cardiac injury by attenuating IL-17A production derived from γδ T cells.

Structured PICO

Does MCTR1 improve cardiac function and reduce inflammation in an LPS-induced endotoxemia mouse model?

Population

Eight-to-twelve-week-old male C57BL/6 mice (weight ~25 g) subjected to an endotoxemia model induced by lipopolysaccharide (LPS).

Intervention

Maresin conjugates in tissue regeneration 1 (MCTR1) 0.15 nmol/mouse administered intravenously via the caudal vein 6 hours after LPS stimulation.

Comparator

Saline control, LPS alone (10 mg/kg intraperitoneal injection), and MCTR1 alone.

Outcome

Cardiac function (left ventricular end-systolic volume, fractional shortening, and ejection fraction) assessed by echocardiography 12 hours after LPS administration.surrogate

MCTR1 improves cardiac function and reduces neutrophil infiltration in LPS-induced cardiac injury via the IL-17 signaling pathway, suggesting a potential therapeutic strategy for sepsis-induced cardiomyopathy.

Abstract

The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC.

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