Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain

Steven T. Dekosky, Scot D. Styren, Mark E. O'Malley, James R. Goss, Patrick Kochanek, Donald Marion, Christopher H. Evans, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Traumatic brain injury (TBI) induces astrocytic and microglial activation and proliferation and augmented production of the cytokine interleukin-1β (IL-1β) and nerve growth factor (NGF). The increase in NGF temporally follows the increase in IL-1β, suggesting that the IL-1β 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-1β and that blocking IL-1β 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.

Original languageEnglish (US)
Pages (from-to)123-127
Number of pages5
JournalAnnals of neurology
Volume39
Issue number1
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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