Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury.
Authors of this article are:
Zhang B, Zhang HX, Shi ST, Bai YL, Zhe X, Zhang SJ, Li YJ.
A summary of the article is shown below:
OBJECTIVE: Inflammation and immune responses are crucial factors associated with the onset and progression of stroke. Interleukin-11 (IL-11) is a hematopoietic IL-6 family cytokine that functions as an anti-inflammatory agent against various inflammatory diseases. However, its roles in stroke remain unknown. In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia.METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels of IL-11 were measured using Western blot analysis, and its location was detected using immunohistochemistry and immunofluorescence staining. The infarct volume was examined using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the neurobehavioral progression was assessed using the neurological scoring system. The expression of astrocytes and microglia was detected using immunochemistry, and real-time quantitative PCR was used for the gene quantification of inflammatory cytokines. The extent of cerebral ischemia-reperfusion injury was tested using Nissl staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of the apoptotic proteins Bax, Bcl-2 and cleaved caspase-3 were detected using Western blot analysis, and the oxidative stress was also measured.RESULTS: The expression of IL-11 mRNA and protein significantly decreased after cerebral ischemia. Immunohistochemical staining showed a large amount of IL-11 in the cerebral cortex of the mice in the vehicle group, whereas the immunoreactivity of IL-11 remained weak for 24 h in the MCAO group. Immunofluorescent staining further confirmed that IL-11 was mainly expressed in the neurons. It was suggested that IL-11 (20 μg/kg) treatment ameliorated infarction and reduced neurological scores. In addition, IL-11 proved to reduce neuropathic damage, glial activation, and the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines after cerebral ischemia. IL-11 was also able to alleviate oxidative stress caused by cerebral ischemia, and AMPK inhibition enhanced the alleviation. Moreover, IL-11 was found to inhibit apoptosis caused by cerebral ischemia, which could also be facilitated by AMPK inhibitors.SIGNIFICANCE: Our research suggests that IL-11 is decreased during cerebral ischemia-reperfusion injury, but IL-11 treatment can improve neurological function and reduce the cerebral infarct volume, which can trigger stroke in mice. AMPK inhibition can further promote the protective effect of IL-11 in stroke. Overall, we demonstrate that IL-11 is of therapeutic interest in controlling stroke and managing cerebral ischemia-reperfusion injury.Copyright © 2019. Published by Elsevier Masson SAS.
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This article is a good source of information and a good way to become familiar with topics such as: AMPK; Cerebral ischemia/reperfusion injury; Inflammatory cytokines; Interleukin-11; Oxidative stress; Stroke.