Central nervous system-initiated inflammation and neurotrophism in trauma:IL-1 beta is required for the production of ciliary neurotrophic factor

Injury to the CNS results in the production and accumulation of inflammator y cytokines within this tissue. The origin and role of inflammation within the CNS remains controversial. In this paper we demonstrate that an acute t rauma to the mouse brain results in the rapid elevation of IL-1 beta, This increase is detectable by 15 min after injury and significantly precedes th e influx of leukocytes that occurs hours after. To confirm that IL-1 beta u p-regulation is initiated by cells within the CNS, in situ hybridization fo r cytokine transcript was combined with cell type immunohistochemistry. The results reveal parenchymal microglia to be the sole source of IL-1 beta at 3 h postinjury, A role for CNS-initiated inflammation was addressed by exa mining the expression of the neurotrophic factor, ciliary neurotrophic fact or (CNTF), Analysis of their temporal relationship suggests the up-regulati on of CNTF by IL-1 beta, which was confirmed through three lines of evidenc e. First, the application of IL-1 receptor antagonist into the lesion site attenuated the up-regulation of CNTF, Second, the examination of corticecto mized animals genetically deficient for IL-1 beta found no CNTF up-regulati on. Third, the lack of CNTF elevation in IL-1 beta null mice was rescued th rough exogenous application of IL-1 beta into the lesion site. These findin gs provide the first evidence of the requirement for IL-1 beta in the produ ction of CNTF following CNS trauma, and suggest that inflammation can have a beneficial impact on the regenerative capacity of the CNS.