Astrocyte-derived Interleukin-31 causes poor prognosis in elderly patients with intracerebral hemorrhage

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH. High concentrations of astrocyte-derived IL31 in the central nervous system (CNS) immune microenvironment of elderly intracerebral hemorrhage (ICH) patients lead to neurological deficits and poor prognosis. The massive activation of astrocytes after ICH in aged mice releases IL31, which binds to microglia indicating that IL31R binds to each other causing massive chemotaxis of microglia. Subsequent activation of N-methyl-D-aspartic acid receptor (NMDA) receptors, P65 and P53, and so forth, causes degenerative changes in neurons, resulting in neuronal apoptosis and leading to a malignant outcome. In contrast, young mice are more inhibited NMDA receptor, P65 and P53, and so forth, which reduce neuronal apoptosis and thus promotes the recovery of neurological function. image