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 ischemi c 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 a ntiinflammatory cytokine that has been shown to reduce inflammation and imp rove functional outcome in human and animal models of inflammatory diseases . We propose the administration of IL-10 following excitotoxic SCI will att enuate the inflammatory response, thus resulting in increased neuronal surv ival. Female, Sprague-Dawley rats were given intraspinal injections of QUIS followed by either intraspinal (5 ng, n = 8) or systemic injections (5 mu g, n = 14) of IL-10. Survival times were varied (2-3 days) in order to prod uce a range of injury states and inflammatory involvement. When administere d 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 divergen t effects were attributed to the modest inflammatory response in the short- term injury compared to the more robust inflammatory response in the more c hronic injury. In conclusion, reducing the inflammatory response to SCI by systemic administration of IL-10 resulted in a significant reduction in neu ronal damage, suggesting that targeting injury-induced inflammation may be an effective treatment strategy for acute SCI. (C) 1999 Academic Press.