IL-37: Novel neuroprotective effects after brain ischemia and reperfusion

Received June 11 2019; Accepted October 17, 2019; Published November 19, 2019
http://dx.doi.org/10.18081/2333-5106/019-298-309

Huang Xiang, Stampf Wael, Kim Jong-Ho, Lee Yang-Jin,  Xiong Xiang, Shan Young-Kyun, Liu Yan, Chung Tae-Young

Abstract

Although IL-37 has many different biological effects in different cells, its main function is to inhibit inflammation. This is achieved through the inactivation of caspase-1, reduction in the production of P2X7 receptor and β-catenin, and inhibition of T cell responses. IL-37 negatively regulates pro-inflammatory cytokines, suppresses T cell proliferation, and inhibits the lack of expression of the MHC class II, CD80, and CD86. Research has also shown that IL-37 may attenuate inflammation, reduce the infarct area, and improve neurologic function during the early stage of brain ischemia and reperfusion. However, the specific mechanism behind this is still not fully understood and requires further study.

The purpose of this study is to provide an overview of IL-37’s ability to reduce inflammation and acute lung injury (ALI) in the early stage of brain ischemia and reperfusion. The study aims to highlight the pathophysiological mechanisms involved and offer a reference framework for the clinical prevention of early ALI after brain ischemic stroke. It should be noted that this study focuses on the innate neuroprotective effects of IL-37 in the brain in response to hypoxia and after brain ischemia and reperfusion in experimental rodent studies. The protective role of endogenous IL-37 has been demonstrated in experimental traumatic brain injury (TBI), ionizing radiation, and kainate-induced seizure mouse models, but will not be included in this review. The pro-survival and inflammation inhibitory molecular mechanisms of IL-37 within the ischemic brain are also not covered in this review paper. The scope of this work is to provide a comprehensive review of IL-37 expression and its associations with ischemia and reperfusion in experimental intraluminal middle cerebral artery occlusion. The study will also include healthy control rodent sham-operated brains for comparison. The aim is to describe the kinetics of IL-37 expression and its antioxidant and anti-inflammatory actions. However, this paper will not provide information about IL-37 as a biomarker or therapeutic agent. The data analysis will provide a rationale for potential IL-37 therapeutic targets and a trajectory for potential lead drug development.

Key words: IL-37, cytokines, chemokines, brain I/R, Bcl-2

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