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

BACKGROUND

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.

METHODS AND

RESULTS

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.

CONCLUSIONS

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.