The proinflammatory cytokine interleukin-1β (IL-1β) is induced rapidly after traumatic brain injury (TBI) and contributes to the inflammatory events that lead to neuronal loss. Although an important source of IL-1β is from the injured brain itself, in patients with multiple organ trauma (polytrauma) IL-1β is also released into the bloodstream which may potentially influence brain vulnerability. The purpose of this study was to determine the effects of systemic inflammation induced by peripheral administration of IL-1β on histopathological and behavioral outcome after moderate fluid percussion (FP) brain injury in rats. At 30 min or 24 hr after TBI, saline, 20μg/kg or 40μg/kg of IL-1β was injected (n=4-9/group) intraperitoneally (IP). Sham operated animals (n=9) received either saline or IL-1β (20 or 40 μg/kg) injections. The somatosensory tactile placing test was administered at 1, 2 and 3 days posttrauma. IL-1β treated animals showed significant placing deficits compared to vehicle-treated TBI animals. Three days after injection, contusion areas and volumes were significantly increased (p<0.05) with both IL-1β doses and at both treatment times compared to vehicle treated animals. IL-1β treated rats showed more contusion injury and hippocampal neuronal damage as well as enhanced perivascular neutrophil accumulation. Cortical IL-1r1 mRNA increased as early as 1 hr following TBI, peaking at 24 hr and remained elevated 3 days posttrauma. These data show that the posttraumatic administration of IL-1β significantly aggravates behavioral outcome and increases overall contusion volume after TBI. Increased systemic inflammatory processes, including extravasation of activated leukocytes and proinflammatory cytokines could participate in this detrimental outcome. Because peripherally circulating cytokines and other neurotoxic factors may be increased following multi-organ trauma, these findings may be important in targeting therapeutic interventions in this patient population.

The early inflammatory response to traumatic brain injury (TBI) may result in secondary damage. The purpose of this study was to evaluate the effects of a transient treatment employing a blocking monoclonal antibody (mAb) to the CD11d/CD18 integrin on histopathological outcome and macrophage infiltration following TBI. A parasagittal fluid percussion (FP) brain injury (1.8 -2.1 atmosphere) was induced in male Sprague-Dawley rats. Rats were randomized into two trauma groups, treated (N=7) and nontreated (N=8) animals. In the treated group, a mAb to the CD11d subunit of the CD11d/CD18 integrin was administered 30 minutes, 24 and 48 hours after brain injury. Control animals received an isotype-matched irrelevant mAb using the same dose and treatment regimen. At three days after TBI, animals were perfusion-fixed for histopathological and immunocytochemical analysis. The anti-CD11d mAb treatment reduced contusion areas as well as overall contusion volume compared to vehicle-treated animals. For example, overall contusion volume was reduced from 2.7 ± 0.5 mm 3 (mean ± SEM) to 1.4 ± 0.4 with treatment (p<0.05). Immunocytochemical studies identifying CD68 immunoreactive macrophages showed that treatment caused significant attenuation of leukocyte infiltration into the contused cortical areas. These data emphasize the beneficial effects of blocking inflammatory cell recruitment into the injured brain on histopathological outcome following traumatic brain injury.

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