Early Immunological Effects of Ischemia-Reperfusion Injury: No Modulation by Ischemic Preconditioning in a Randomised Crossover Trial in Healthy Humans.

Thomas H Lange,Bo Martin Bibby,Bente Jespersen,Bjarne K Møller,Marco Eijken,Carla Baan,Mikkel Steen Petersen

doi:10.3390/ijms20122877

Abstract

Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. IPC and IRI were performed by cuff inflation on the forearm. IPC consisted of four cycles of five minutes followed by five minutes of reperfusion. IRI consisted of twenty minutes followed by 15 min of reperfusion. Blood was collected at baseline, 0 min, 85 min and 24 h after IRI. Circulating monocytes, T-cells subsets and dendritic cells together with intracellular activation markers were quantified by flow cytometry. Luminex measured a panel of inflammation-related cytokines in plasma. IRI resulted in dynamic regulations of the measured immune cells and their intracellular activation markers, however IPC did not significantly alter these patterns. Neither IRI nor the IPC protocol significantly affected the levels of inflammatory-related cytokines. In healthy volunteers, it was not possible to detect an effect of the investigated IPC-protocol on early IRI-induced inflammatory responses. This study indicates that protective effects of IPC on IRI is not explained by direct modulation of early inflammatory events.

Highlights

Organ lesions related to ischemia-reperfusion injury (IRI) are common and pose important clinical problems
This study indicates that protective effects of Ischemic preconditioning (IPC) on IRI is not explained by direct modulation of early inflammatory events
This study evaluated the effects of IPC on IRI by analysing circulating immune cell subsets, intracellular activation markers and inflammatory-related cytokine levels, using a randomised controlled crossover trial in healthy participants

Summary

Introduction

Organ lesions related to ischemia-reperfusion injury (IRI) are common and pose important clinical problems. IRI is the background for, e.g., myocardial infarctions, strokes, and acute kidney injury including that seen in 30–80% of patients after deceased donor kidney transplants. Circulating immune cells such as T cells are known to influence IRI [1]. This includes T helper cell type 1 and 17 (Th1 and Th17), whereas the presence of regulatory T cells (Tregs) is associated with better outcome after IRI [1,2,3,4]. IRI is associated with a pro-inflammatory immune response [5]. Cytokines are major signalling molecules, that tightly regulate the inflammatory process in the immune system, whereas IL1, IL6, IL17, TNFα and INFγ are mainly pro-inflammatory signalling and IL10 are more anti-inflammatory signalling [6]

Methods

Results

Conclusion