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

Background: Interferon (IFN)-beta 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-beta, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-beta 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-beta or its receptor, the IFN-alpha/beta 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-beta knockout (IFN-beta KO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-beta KO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-beta KO 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-beta KO mice further supports an important immunoregulatory function of IFN-beta 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-beta KO group, while endogenous IFN-beta signaling did not affect the infarct volume. Conclusions: We conclude that endogenous IFN-beta signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome.