Absence of IL-1 beta 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-1 beta acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1 beta in axonal plasticity. Here, we have investigated the effects of IL-1 beta 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-1 beta deficiency model (IL-1 beta KO mice) and administered recombinant IL-1 beta. 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-1 beta. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1 beta in IL-1 beta KO 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-1 beta KO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1 beta not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.