The effects of endogenous interleukin-10 on gray matter damage and the development of pain behaviors following excitotoxic spinal cord injury in the mouse.
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.
Abraham
K E
KE
Division of Physical Therapy, Shenandoah University, 333 West Cork Street, Winchester, VA 22601, USA. kabraham@su.edu
McMillen
D
D
Brewer
K L
KL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001772:Blood Cell Count; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins; D010146:Pain / Q000523:psychology*; D010487:Periaqueductal Gray / Q000473:pathology*; D013118:Spinal Cord Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology*
D018696:Neuroprotective Agents; D009498:Neurotoxins; D016753:Interleukin-10