The effects of endogenous interleukin-10 on gray matter damage and the development of pain behaviors following excitotoxic spinal cord injury in the mouse.

Abstract

Interleukin-10 (IL-10) has been utilized as a neuroprotective agent in experimental models of spinal cord injury because of its potent anti-inflammatory properties. Previous studies have delivered a single dose (5 microg) of IL-10 following experimental spinal cord injury in the rat, and demonstrated various degrees of neuroprotection. However, the role of endogenous production of IL-10 has not been considered. Therefore, the purpose of the current study was to establish the role of endogenous IL-10 and demonstrate the true potential of exogenous IL-10 administration through the use of IL-10((-/-)) mice. Using the quisqualic acid model of spinal cord injury, we examined the extent of gray matter damage and onset of injury-induced pain behaviors at various time points following injury in wild-type vs. IL-10((-/-)) mice. Additionally, IL-10 was reconstituted in IL-10 deficient mice by the intraperitoneal administration of 50 ng recombinant murine (rm) IL-10 30 min following quisqualic acid injection. Animals were observed daily following injury for the onset of pain-behaviors. At days 1, 7, and 14 following injection, lesion analysis revealed a greater extent of damage at early time points (1 day, 7 days) following injury in the IL-10((-/-)) animals as compared with wild-type animals. However, by 14 days post-experimental spinal cord injury, the extent of damage between the two groups was not significant. IL-10((-/-)) animals that received the single (50 ng) rmIL-10 injection following injury displayed gray matter damage patterns similar to wild-type animals. The pronounced early damage noted in the IL-10((-/-)) animals was associated with an approximately two-fold increase in peripheral neutrophils, an index of an innate immune response to injury, compared with wild-type mice. In addition, wild type and IL-10((-/-)) animals receiving rmIL-10 demonstrated a delay in the onset of injury-induced pain behaviors. However, by 14 days post-experimental spinal cord injury the overall incidence of pain behaviors was similar between all treatment groups. Therefore, the absence of IL-10 expression accelerates the kinetics of lesion expansion, the onset of pain behaviors, and the peripheral immune response to spinal cord injury. Endogenous IL-10 and low doses of exogenous IL-10 are neuroprotective at 1 and 7 days following injury. Therefore, the results of the current study suggest that low dose IL-10 administration acutely following spinal cord injury has potential as a therapeutic agent for limiting tissue loss following injury.

• Authors: K E Abraham, D McMillen, K L Brewer
• Journal: Neuroscience (Neuroscience) Vol. 124 Issue 4 Pg. 945-52 ( 2004) ISSN: 0306-4522 [Print] United States
• PMID: 15026134 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Neurotoxins
• Interleukin-10

Topics

• Animals
• Behavior, Animal (drug effects)
• Blood Cell Count
• Interleukin-10 (metabolism, pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuroprotective Agents (metabolism, pharmacology)
• Neurotoxins
• Pain (psychology)
• Periaqueductal Gray (pathology)
• Spinal Cord Diseases (blood, chemically induced, pathology, psychology)