title: Intracerebral interleukin-10 injection modulates post-ischemic neuroinflammation: an experimental microarray study.
abstract: Stroke induces a profound neuroinflammatory reaction that leads to secondary cerebral tissue injury. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that is endogenously produced by immune cells and limits this inflammatory reaction. Previously, therapeutic administration of IL-10 has been shown to be neuroprotective in experimental stroke. However, the signaling pathways affected by this approach are largely unknown. The aim of this study was to verify the neuroprotective effects of IL-10 in an experimental mouse stroke model and to analyze the pathways modulated by this approach. Therefore, we performed a whole genome microarray analysis comparing the cerebral gene expression profile at two time points after cortical stroke in IL-10-treated and control C57Bl/6J mice. We administered IL-10 locally by intracerebroventricular injection. We were able to validate a reduction of infarct volume by IL-10 administration and characterized the kinetics of endogenous cerebral IL-10 expression after stroke. The microarray analysis revealed that IL-10 treatment effectively downregulated pro-inflammatory signaling cascades which were upregulated by the ischemic lesion in the acute phase after the stroke. This is the first study characterizing the global gene regulation profile of IL-10 immunotherapy for ischemic stroke. Our results emphasize the key role of IL-10 as a neuroprotective cytokine and suggest several novel downstream pathways for further investigation to better understand the mechanisms of post-stroke neuroinflammation.
authors.affiliation: Department of Neurology, University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Max-Lebsche-Platz 30, 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address: Arthur.Liesz@med.uni-muenchen.de.
authors.forename: Arthur
authors.initials: A
authors.lastname: Liesz
authors.affiliation: Division of Functional Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Division of Functional Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Hoheisel
authors.affiliation: Department of Neurology, University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; Division of Brain Sciences, Imperial College London, Fulham Palace Road, London W6 RF, UK.
authors.forename: Roland
authors.initials: R
authors.lastname: Veltkamp
mesh_terms: D000210:Acute-Phase Reaction / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control*; D007276:Injections, Intraventricular; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020521:Stroke / Q000150:complications*
chemical_list: D018696:Neuroprotective Agents; D016753:Interleukin-10
keywords: Experimental brain ischemia; Interleukin-10; Microarray; Neuroinflammation; Stroke