Systemically administered interleukin-10 reduces tumor necrosis factor- alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats

John R Bethea, Hideki Nagashima, Marcia C. Acosta, Carmen Briceno, Frankie Gomez, Alexander E. Marcillo, Kim Loor, Jeremy Green, W. Dalton Dietrich

Research output: Contribution to journalArticle

305 Scopus citations

Abstract

In these studies, we examined the neuroprotective effects of the potent antiinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury (SCI). Neuroprotection was assessed by using behavioral and morphological end points. We hypothesized that injury-induced inflammation contributes to the resulting neuropathology and subsequent loss of function. Therefore, by attenuating injury-induced inflammation, we should promote functional recovery. The New York University device was used to induce moderate SCI and study the resulting inflammatory response and functional consequences of inhibiting this response in rats. We determined that SCI induces the expression of tumor necrosis factor-alpha (TNF-α) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 μg) administered 30 minutes after-injury significantly reduced the expression of TNF-α protein in the spinal cord and in vitro by SCI-activated monocytes. Next, we investigated whether IL-10 would improve functional recovery after SCI. Randomized, double-blinded studies demonstrated that a single injection of IL-10 significantly improves hind limb motor function 2 months after injury, as determined by the Basso, Beattie and Bresnahan (BBB) open-field behavioral test. IL-10-treated animals had a mean BBB score of 18.0 ± 0.5 (SEM, n = 9) compared with a score of 12.9 ± 0.6 (SEM, n = 9) for the saline-treated controls. Morphological analysis demonstrated that IL- 10 reduces lesion volume by approximately 49% 2 months after injury. These data suggest that acute administration of IL-10 reduces TNF-α synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.

Original languageEnglish (US)
Pages (from-to)851-863
Number of pages13
JournalJournal of neurotrauma
Volume16
Issue number10
DOIs
StatePublished - Oct 1999

Keywords

  • Axonal growth
  • Inflammation; behavioral recovery
  • Interleukin-10
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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