Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats
Jr. Bethea et al., Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats, J NEUROTRAU, 16(10), 1999, pp. 851-863
In these studies, we examined the neuroprotective effects of the potent ant
iinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury
(SCI). Neuroprotection was assessed by using behavioral and morphological e
nd 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 reco
very. The New York University device was used to induce moderate SCI and st
udy the resulting inflammatory response and functional consequences of inhi
biting this response in rats. We determined that SCI induces the expression
of tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and by SCI-a
ctivated monocytes isolated from the peripheral circulation. IL-10 (5.0 mu
g) administered 30 minutes after-injury significantly reduced the expressio
n of TNF-alpha protein in the spinal cord and in vitro by SCI-activated mon
ocytes. Next, we investigated whether IL-10 would improve functional recove
ry after SCI. Randomized, double-blinded studies demonstrated that a single
injection of IL-10 significantly improves hind limb motor function 2 month
s after injury, as determined by the Basso, Beattie and Bresnahan (BBB) ope
n-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) fo
r 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-alpha synthesis
in the spinal cord and by activated macrophages, is neuroprotective, and p
romotes functional recovery following SCI.