AJBM Volume 2, Issue 1, pages 113–123, January 2014
Huang Xiang, Stampf Wael, Kim Jong-Ho, Lee Yang-Jin, Xiong Xiang, Shan Young-Kyun, Liu Yan, Chung Tae-Young
Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. IL-37 (IL-37), a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. The purpose of the present study was to determine the effects of interleukin-37 on neuron cells and on brain inflammation induced by brain ischemia/reperfusion (I/R). A transgenic mouse strain was generated to express human IL-37 (hIL-37Tg) and WT mice were subjected to (60 min) brain ischemia and followed by reperfusion (24 h), by using a mice model of transient focal cerebral ischemia induced by advancing a nylon mono-filament to occlude the middle cerebral artery (MCA). Infarct size was determined by triphenyltetrazolium chloride staining. The morphology of neurons in brain sections were examined by Nissl staining and cytokines/chemokines measured by ELIZA. IL-37Tg significantly reduced infarct size by 65.4% (P<0.05) compared with WT after I/R. Reduced inflammation was associated with decreased leukocyte recruitment, and reduced release of IL-1β and TNFα, macrophage inflammatory protein-2 (MIP-2), MCP-1 and keratinocyte chemokine (KC) compared with WT (P<0.05), whereas IL-10 was increased eight fold (P<0.05). IL-37 significantly reduced cell death and increased Bcl-2 expression in neurons. Thus, IL-37 emerges as a key modulator of brain inflammation and has important translational implications for both the prevention and treatment of patients suffering from brain ischemia.
Key words: IL-37, cytokines, chemokines, brain I/R, Bcl-2