Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain.
Traumatic brain injury (TBI) induces astrocytic and microglial activation and proliferation and augmented production of the cytokine interleukin-1 beta ( IL-1 beta) and nerve growth factor ( NGF). The increase in NGF temporally follows the increase in IL-1 beta, suggesting that the IL-1 beta up-regulation after trauma directly induces the increase in NGF. We examined the effect of IL-1 receptor antagonist protein ( IL-1ra) on microglial proliferation and NGF production in rat cortex, following two different models of TBI. Rabbit fibroblasts infected with a retroviral vector containing the human IL-1ra gene were implanted into the wound cavity immediately following a cortical stab wound or 6 hours after a weight drop-induced trauma. Both microglial proliferation and NGF up-regulation were decreased significantly in animals receiving IL-1ra-expressing cells compared with animals receiving naive (untransfected) fibroblasts. These data demonstrate that the increase in NGF after central nervous system trauma is directly mediated through IL-1 beta and that blocking IL-1 beta following brain injury leads to suppression of an NGF-mediated reparative response. Such blockade of inflammation, however, may prove to be of significant therapeutic benefit in human brain injury and other inflammatory states.[1]References
- Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain. DeKosky, S.T., Styren, S.D., O'Malley, M.E., Goss, J.R., Kochanek, P., Marion, D., Evans, C.H., Robbins, P.D. Ann. Neurol. (1996) [Pubmed]
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