INTERLEUKIN-10 IMPROVES OUTCOME AND ALTERS PROINFLAMMATORY CYTOKINE EXPRESSION AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY

Traumatic injury to the central nervous system initiates inflammatory processes that are implicated in secondary tissue damage. These proces ses include the synthesis of proinflammatory cytokines, leukocyte extr avasation, vasogenic edema, and blood-brain barrier breakdown. Interle ukin-10 (IL-10), a cytokine with antiinflammatory properties, negative ly modulates proinflammatory cascades at multiple levels. We examined the hypothesis that IL-10 treatment can improve outcome in a clinicall y relevant model of traumatic brain injury (TBI). IL-10 was administer ed via different routes and dosing schedules in a lateral fluid-percus sion model of TBI in rats. Intravenous administration of IL-10 (100 mu g) 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 expres sion in the injured hippocampus, and to a lesser extent, in the injure d cortex. Subcutaneous IL-10 administration (100 mu g) at 10 min, 1, 3 , 6, 9, and 12 h after TBI also enhanced neurological recovery. In con trast, intracerebroventricular administration of IL-10 (1 or 6 mu g) a t 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 proinflamm atory cytokine synthesis. (C) 1998 Academic Press.