Table 1.

Comparison of studies on IL-33 in traumatic brain injury involved in the review.

Study type	Study design	Conclusion	Reference
Original article	A blunt, weight-drop approach to model TBI in mice.	It was shown that TBI causes the elevation of IL-33, IL-1β, IL-38, TNF-α, IFN-α, and IL-19 in the hippocampus at 3 h time point, and concomitant EI results in the dose-dependent downregulation of IL-33, IL-1β, IL-38, TNF-α, IFN-α, and IL-19.	[24]
Original article	Spinal cord of mice was damaged, and recombinant IL-33 was injected.	Addition of wild-type lung-derived ILC2s into the meningeal space of IL-33r-/- animals partially improves recovery after spinal cord injury. IL-33 released after CNS injury not only initiates a local response but also a meningeal one through actions of ILC2s.	[29]
Comment	Comment on “The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury” by Gadani SP, Walsh, J. T., Smirnov, I., Zheng, J. and Kipnis, J. published in neuron in 2015.	Administration of recombinant IL-33 might be beneficial for treating TBI.	[1]
Original article	Transient focal ischemia was induced by intraluminal occlusion of the left middle cerebral artery for 1 h with silicone-coated sutures in mice.	IL-33/ST2 signaling was described as a potential immune regulatory mechanism that enhances the expression of IL-10 in M2 microglia and reduces acute ischemic brain injury after stroke.	[28]
Original article	Serum ST2 concentrations in 106 healthy controls and 106 severe TBI patients were measured.	Serum ST2 concentrations are significantly related to inflammation. In TBI, it may be a potential diagnostic marker.	[14]
Original article	Samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of CNS injury were used.	IL-33 plays a role in neuroinflammation, and microglia/macrophages are cellular targets for this IL following TBI.	[30]