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1 Cardiovascular Surgery, Hospital for Sick Children, Toronto, ON, Canada
2 Cardiology, Heart and Stroke Richard Lewar Centre of Excellence, Toronto, ON, Canada
3 Addenbrooke's Centre of Clinical Investigations, University of Cambridge, Canbridge, UK, United Kingdom
4 Cardiology, Hospital for Sick Children, Toronto, ON, Canada
5 Respirology, University of Toronto, Toronto, ON, Canada
* To whom correspondence should be addressed. E-mail: andrew.redington{at}sickkids.ca.
<Background: Remote ischemic preconditioning (IPC) reduces tissue injury caused by ischemia-reperfusion (IR) in distant organs. We tested the hypothesis that remote IPC modifies inflammatory gene transcription in humans. Methods and Results: Using a microarray method, we demonstrated that a simple model of brief forearm ischemia suppresses pro-inflammatory gene expression in circulating leukocytes. Genes encoding key proteins involved in cytokine synthesis, leukocyte chemotaxis, adhesion and migration, exocytosis, innate immunity signaling pathways and apoptosis were all suppressed within 15 minutes (early phase IPC) and more so after 24 hours (second window IPC). Changes in leukocyte CD11b expression measured by flow cytometry mirrored this pattern, there being a significant (p=0.01) reduction at 24 hours. Conclusion: The results of this study show that the remote IPC stimulus modifies leukocyte inflammatory gene expression. This effect may contribute to the protective effect of IPC against IR injury, and may have broader implications in other inflammatory processes.
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