Endogenous IFN-[beta] 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. Keywords: Cytokines, IFN-[alpha]/[beta] receptor, Interferon-[beta], Inflammatory and immune cells, Knockout mice, Middle cerebral artery occlusion