IL-37 increases in patients after ischemic stroke and protects from inflammatory brain injury, motor impairment and lung infection in mice

Shenpeng R. Zhang, Marcel F. Nold, Sung Chun Tang, Christine B. Bui, Claudia A. Nold, Thiruma V. Arumugam, Grant R. Drummond, Christopher G. Sobey, Hyun Ah Kim

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Post-stroke inflammation may contribute to secondary brain injury and systemic immunosuppression. Interleukin(IL)-37 is an immunosuppressive cytokine belonging to the IL-1 superfamily with no mouse homologue yet identified, the effects of which have not been studied in stroke. Here we report: (1) the effect of ischemic stroke on circulating IL-37 in humans; and (2) the effect of IL-37 on stroke outcome measures in mice transgenic for human IL-37 (IL-37tg). We found that in the first 3 days after ischemic stroke in 55 patients, the plasma abundance of IL-37 was ~2-fold higher than in 24 controls. In IL-37tg mice, cerebral ischemia-reperfusion resulted in marked increases in plasma IL-37 (~9-fold) and brain IL-37 mRNA (~7,000-fold) at 24 h compared with sham-operated IL-37tg mice. Further, compared with wild-type (WT) mice subjected to cerebral ischemia-reperfusion, IL-37tg mice exhibited less severe locomotor deficit, smaller cerebral infarcts and reduced bacterial lung infection. In the ischemic hemisphere, there were 60% fewer pro-inflammatory microglia-macrophages and up to 4-fold higher expression of anti-inflammatory markers in IL-37tg compared to WT mice. Our data show that IL-37 expression is increased following ischemic stroke in humans and IL-37tg mice, and may exert protective effects by modulating post-stroke inflammation in the brain and periphery.

Original languageEnglish
Article number6922
Number of pages12
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2019

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