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

•Focal cerebral ischemia/reperfusion may stimulate rapid and long-term Th1 and Th17 immune responses.•The reduction of IL-33 expression may be associated to the status of Th1/Th2 imbalance after ischemic stroke.•Recombinant mouse IL-33 could ameliorate the severity of ischemic brain injury after MCAO.•The protective effect of IL-33 may be related to promoting Th2 response and suppressing Th17 response.•IL-33 may be a new target for therapy of ischemic stroke.

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 6 h after transient cerebral ischemia/reperfusion even up to day 3. Meanwhile, the protein and mRNA level of IL-33 expression was significantly decreased at 6 h and 72 h, but not at 24 h after MCAO. Moreover, recombinant mouse IL-33 administration substantially attenuated ischemic brain damage and neurological deficit at 24 h and 72 h, but not at 6 h 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.