Article Impact Level: HIGH Data Quality: STRONG Summary of Cell, S0092867424007025. https://doi.org/10.1016/j.cell.2024.06.028 Dr. Alba Simats et al.
Points
- Post-stroke complications may stem from prolonged pro-inflammatory alterations in monocytes/macrophages across multiple organs, persisting up to three months after the stroke.
- These immune changes lead to cardiac fibrosis and dysfunction, as observed in both experimental mice and human stroke patients.
- IL-1β is identified as a critical mediator driving these epigenetic changes associated with innate immune memory, contributing to chronic post-stroke comorbidities.
- Blocking IL-1β or pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor prevented post-stroke cardiac dysfunction in experimental models, suggesting potential therapeutic strategies.
- Targeting specific immune components, such as IL-1β and monocyte trafficking, could form the basis of innovative strategies to reduce chronic diseases following a stroke, extending the therapeutic window beyond acute management to improve patient outcomes.
Summary
The long-term effects of acute brain ischemia extend significantly beyond the initial brain injury, potentially causing chronic systemic illnesses due to altered immune responses. A recent study explored the hypothesis that post-stroke complications might originate from a shared immunological mechanism. Using single-cell sequencing, researchers discovered prolonged pro-inflammatory alterations in monocytes/macrophages across multiple organs, persisting for up to three months post-stroke. These changes were particularly evident in the heart, where they led to cardiac fibrosis and dysfunction, observable both in experimental mice and human stroke patients. IL-1β was pinpointed as a critical mediator, driving these epigenetic changes associated with innate immune memory.
Further investigation into the mechanisms underlying these immune alterations revealed that the epigenetic changes induced by IL-1β in monocytes/macrophages could be transferred to naive mice, resulting in cardiac dysfunction. This finding underscores the role of innate immune memory in mediating chronic post-stroke comorbidities and highlights the potential of targeting these pathways for therapeutic intervention. In experimental models, the application of an IL-1β neutralizing agent or the blockade of pro-inflammatory monocyte trafficking via a CCR2/5 inhibitor successfully prevented the development of post-stroke cardiac dysfunction. This suggests that modulating the immune response after a stroke may offer protective benefits against secondary comorbidities.
The study provides compelling evidence that targeting specific components of the immune system, such as IL-1β and monocyte trafficking, could form the basis of innovative secondary prevention strategies in stroke patients. By focusing on the immunological links to post-stroke complications, such interventions aim to reduce the burden of chronic diseases that often accompany cerebrovascular accidents. This approach holds promise for extending the therapeutic window beyond acute stroke management to potentially improve overall patient outcomes and quality of life.
Link to the article: https://www.cell.com/cell/fulltext/S0092-8674(24)00702-5
References Simats, A., Zhang, S., Messerer, D., Chong, F., Beşkardeş, S., Chivukula, A. S., Cao, J., Besson-Girard, S., Montellano, F. A., Morbach, C., Carofiglio, O., Ricci, A., Roth, S., Llovera, G., Singh, R., Chen, Y., Filser, S., Plesnila, N., Braun, C., … Liesz, A. (2024). Innate immune memory after brain injury drives inflammatory cardiac dysfunction. Cell, S0092867424007025. https://doi.org/10.1016/j.cell.2024.06.028
