Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats.
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-alpha) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 microg) administered 30 minutes after-injury significantly reduced the expression of TNF-alpha 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-alpha synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.
Bethea
J R
JR
The Miami Project to Cure Paralysis and the Department of Neurological Surgery, University of Miami School of Medicine, Florida, USA. jbethea@miamiproj.med.miami.edu
Nagashima
H
H
Acosta
M C
MC
Briceno
C
C
Gomez
F
F
Marcillo
A E
AE
Loor
K
K
Green
J
J
Dietrich
W D
WD
D000818:Animals; D005260:Female; D006614:Hindlimb / Q000294:innervation; D007249:Inflammation; D016753:Interleukin-10 / Q000627:therapeutic use*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10