Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response.

Ischemic stroke causes brain injury with activation of an inflammatory response that can contribute to clinical impairment. As a novel cytokine of the interleukin-1 (IL-1) family, IL-33 has been suggested to be involved in regulating pathophysiology and inflammatory responses in the central nervous system (CNS). However, the role and underlying mechanisms of IL-33 in ischemic stroke remain poorly understood. Here, adult male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) for stroke induction. The MCAO procedure resulted in the enhanced Th1 and Th17 immune responses from 6h after transient cerebral ischemia/reperfusion even up to day 3. Meanwhile, the protein and mRNA level of IL-33 expression was significantly decreased at 6h and 72 h, but not at 24h after MCAO. Moreover, recombinant mouse IL-33 administration substantially attenuated ischemic brain damage and neurological deficit at 24h and 72 h, but not at 6h after MCAO. Interestingly, the reduced CNS inflammation in IL-33-treated MCAO mice may be at least partly due to an induced immuno-shift of Th cells from Th1 to Th2 response and suppressing Th17 immune response. These findings demonstrate that IL-33 can play a protective role after MCAO and may be a new target for therapy of ischemic stroke.