Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

Background: interferon (ifn)-β exerts anti-inflammatory effects,coupled to remarkable neurological improvements in multiple sclerosis,a neuroinflammatory condition of the central nervous system. analogously,it has been hypothesized that ifn-β,by limiting inflammation,decreases neuronal death and promotes functional recovery after stroke. however,the core actions of endogenous ifn-β signaling in stroke are unclear. methods: to address this question,we used two clinically relevant models of focal cerebral ischemia,transient and permanent middle cerebral artery occlusion,and two genetically modified mouse lines,lacking either ifn-β or its receptor,the ifn-α/β receptor. subsets of inflammatory and immune cells isolated from the brain,blood,and spleen were studied using flow cytometry. sensorimotor deficits were assessed by a modified composite neuroscore,the rotating pole and grip strength tests,and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. results: here,we report alterations in local and systemic inflammation in ifn-β knockout (ifn-βko) mice over 8 days after induction of focal cerebral ischemia. notably,ifn-βko mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. concomitantly,in the blood of ifn-βko mice,we found a higher percentage of total b cells but a similar percentage of mature and activated b cells,collectively indicating a higher proliferation rate. the additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and ifn-βko mice further supports an important immunoregulatory function of ifn-β in stroke. moreover,we observed a significant weight loss 2-3 days and a reduction in grip strength 2 days after stroke in the ifn-βko group,while endogenous ifn-β signaling did not affect the infarct volume. conclusions: we conclude that endogenous ifn-β signaling attenuates local inflammation,regulates peripheral immune cells,and,thereby,may contribute positively to stroke outcome. © 2015 inácio et al.