title: Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury.
abstract: Traumatic injury to the central nervous system initiates inflammatory processes that are implicated in secondary tissue damage. These processes include the synthesis of proinflammatory cytokines, leukocyte extravasation, vasogenic edema, and blood-brain barrier breakdown. Interleukin-10 (IL-10), a cytokine with antiinflammatory properties, negatively modulates proinflammatory cascades at multiple levels. We examined the hypothesis that IL-10 treatment can improve outcome in a clinically relevant model of traumatic brain injury (TBI). IL-10 was administered via different routes and dosing schedules in a lateral fluid-percussion model of TBI in rats. Intravenous administration of IL-10 (100 micrograms) at 30 min before and 1 h after TBI improved neurological recovery and significantly reduced TNF expression in the traumatized cortex at 4 h after injury. Such treatment was associated with lower IL-1 expression in the injured hippocampus, and to a lesser extent, in the injured cortex. Subcutaneous IL-10 administration (100 micrograms) at 10 min, 1, 3, 6, 9, and 12 h after TBI also enhanced neurological recovery. In contrast, intracerebroventricular administration of IL-10 (1 or 6 micrograms) at 15 min, 2, 4, 6, and 8 h after TBI was not beneficial. These results indicate that IL-10 treatment improves outcome after TBI and suggest that this improvement may relate, in part, to reductions in proinflammatory cytokine synthesis.
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Knoblach
authors.forename: A I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10