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Research Article: Systemic inflammatory response drives post-cardiac arrest multi-organ injury via IL-17 signaling in murine and porcine models

Date Published: 2026-04-29

Abstract:
Systemic inflammation plays a central role in the development of multi-organ diseases. Post-cardiac arrest syndrome (PCAS) is increasingly recognized as a systemic inflammatory condition characterized by myocardial dysfunction, brain injury, and multi-organ dysfunction following resuscitation. Interleukin-17 signaling is an important proinflammatory pathway, but its specific role in the pathogenesis of PCAS remains unclear. Using transcriptomic profiling of both cardiac and cerebral tissues after cardiac arrest/cardiopulmonary resuscitation (CA/CPR), we found that myocardial dysfunction and brain injury were associated with early activation of the IL-17 signaling pathway during the post-resuscitation period. Further analysis of differentially expressed genes identified interleukin-17A (IL-17A) as a critical cytokine driving systemic inflammation and subsequent cardiac and cerebral dysfunction following CA/CPR. Consistently, plasma IL-17A levels were significantly elevated in patients who experienced CA after myocardial infarction compared with non-CA controls. Early inhibition of IL-17A with secukinumab in both murine and porcine models of CA/CPR significantly attenuated PCAS, including improved left ventricular ejection fraction, reduced neuronal apoptosis, and improved 72-hour survival (all P < 0.05), demonstrating multi-organ protective effects. These findings demonstrate that CA induces a systemic inflammatory response that drives heart–brain injury and multi-organ dysfunction, and IL-17A acts as an inflammatory mediator in this process. Targeting of IL-17A may represent a potential therapeutic strategy for inflammation-driven multi-organ injury after CA.

Introduction:
Systemic inflammation plays a central role in the development of multi-organ diseases. Post-cardiac arrest syndrome (PCAS) is increasingly recognized as a systemic inflammatory condition characterized by myocardial dysfunction, brain injury, and multi-organ dysfunction following resuscitation. Interleukin-17 signaling is an important proinflammatory pathway, but its specific role in the pathogenesis of PCAS remains unclear.

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