Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury.
Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Inflammatory responses appear to be a major component of the secondary neuronal injury initiated by SCI and play a role in the pathogenesis of QUIS-induced injury. IL-10 is a potent antiinflammatory cytokine that has been shown to reduce inflammation and improve functional outcome in human and animal models of inflammatory diseases. We propose the administration of IL-10 following excitotoxic SCI will attenuate the inflammatory response, thus resulting in increased neuronal survival. Female, Sprague-Dawley rats were given intraspinal injections of QUIS followed by either intraspinal (5 ng, n = 8) or systemic injections (5 microgram n = 14) of IL-10. Survival times were varied (2-3 days) in order to produce a range of injury states and inflammatory involvement. When administered intraspinally, IL-10 significantly exacerbated the QUIS damage (P < 0.05), resulting in an 11.2% increase in lesion volume. When given systemically, IL-10 significantly decreased lesion volume by 18.1% in the more advanced injury (P < 0.05), but did not effect the more acute injury. These divergent effects were attributed to the modest inflammatory response in the short-term injury compared to the more robust inflammatory response in the more chronic injury. In conclusion, reducing the inflammatory response to SCI by systemic administration of IL-10 resulted in a significant reduction in neuronal damage, suggesting that targeting injury-induced inflammation may be an effective treatment strategy for acute SCI.
Brewer
K L
KL
Department of Anatomy and Cell Biology, East Carolina University, 27858, USA.
Bethea
J R
JR
Yezierski
R P
RP
D000818:Animals; D003643:Death; D005260:Female; D006801:Humans; D007249:Inflammation; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000008:administration & dosage / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000473:pathology; D016318:Quisqualic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D018696:Neuroprotective Agents; D009498:Neurotoxins; D016753:Interleukin-10; D016318:Quisqualic Acid