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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.

Inflammatory cascades are increasingly recognized as an important pathophysiological mechanism in intracerebral hemorrhage (ICH). In contrast, the effect of ICH on the systemic immune system has barely been investigated. We examined the effects of different hematoma volumes on immune cell subpopulations in experimental murine ICH. In C57BL/6 mice, ICH was induced by striatal injection of autologous blood (10, 30 or 50 μL). Control animals received the respective sham operation. Three days after ICH induction, differential blood leukocyte counting was performed. Lymphocyte subpopulations were further characterized by flow cytometry in blood, spleen, lymph node and thymus. Infectious complications were studied using microbiological cultures of blood and lungs. Only after large ICH a marked decrease of leukocyte counts and most lymphocyte subsets was observed in all organs. Despite this general leukocytopenia, a significant, up to 10-fold increase, was detected in the monocyte population after extensive hemorrhage. After moderate ICH induction, only specific lymphocyte subpopulations were differentially affected. Mature thymic cells were unaffected while immature CD4+CD8+ cells were depleted by over 90% after large ICH. A significant proportion of mice with extensive ICH (36.4%) developed spontaneous pneumonia and/or bacteremia while none of the sham operated mice had infectious complications. The ICH size determines the extent of systemic immunomodulation. Large ICH predisposes animals to infections.