Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury

Abstract

Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI). We used an IL-1β deficiency model (IL-1βKO mice) and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

“…For example, the spinal cord mRNA levels of interleukin-1b (IL-1b) increase 12 hours after SCI; 26 72 hours after injury treated with IL-1 receptor antagonist, the contusion-induced apoptosis was significantly reduced. 27 This result showed that IL-1b is harmful to tissue at the early stage. Macrophages are the main source of IL-1b.…”

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury

“…29 Absence of IL-1β inhibits lesion development and axonal plasticity and exerts positive effects on neurological outcome. 30 Blocking the IL-1 receptor suppresses microglial activation, promotes ventral horn neuron survival, 31 attenuates the severity of spinal cord 32 and promotes neurological recovery after SCI. 33 IL-18 is another kind of important proinflammatory cytokine after SCI.…”

Hypoxic postconditioning reduces microglial activation, astrocyte and caspase activity, and inflammatory markers after hypoxia–ischemia in the neonatal rat brain

“…Therefore, it is likely that the lower levels of TNF-α and IL-1β we observed 5 d after HI had already started going down, suggesting that we might have missed the peak of release of both cytokines. Higher levels of proinflammatory cytokines are likely to exacerbate brain injury processes, where increased IL-1β and exogenous TNF-α relate to worse outcomes in rodent stroke models (5,38). IL-1β knockout mice demonstrate reduced injury and axonal plasticity after a spinal cord injury (38), and blocking TNF-α offers neuroprotection against inflammatory and excitotoxic insults in neonatal rats (5).…”

“…Higher levels of proinflammatory cytokines are likely to exacerbate brain injury processes, where increased IL-1β and exogenous TNF-α relate to worse outcomes in rodent stroke models (5,38). IL-1β knockout mice demonstrate reduced injury and axonal plasticity after a spinal cord injury (38), and blocking TNF-α offers neuroprotection against inflammatory and excitotoxic insults in neonatal rats (5). The anti-inflammatory strategy of using minocycline can reduce levels of TNF-α and IL-1β and protect against HI brain injury in the preterm rat neonate (6).…”