In vivo neutralization of endogenous brain fractalkine increases hippocampal TNF alpha and 8-isoprostane production induced by intracerebroventricular injection of LPS

Fractalkine is a chemokine widely and constitutively expressed in the brain and, as suggested by in vitro studies, it is involved in brain inflammator y responses. In this study, we have investigated the in vivo anti-inflammat ory potential of fractalkine in a model of neuroinflammation induced by int racerebroventricular injection of lipopolysaccharide (LPS) in rats. LPS ind uces a rapid and acute production of the pro-inflammatory cytokine, TNF alp ha, in hippocampus and cerebrospinal fluid (CSF), and an increase of 8-isop rostane levels, a marker of oxidative stress, in hippocampus. Although intr acerebroventricular injection of fractalkine has no effect on TNF alpha and 8-isoprostane production, neutralization of endogenous fractalkine within the brain with a specific anti-fractalkine antibody potentiates LPS effects . These data emphasize the involvement of constitutive brain fractalkine in the control of inflammatory reaction in CNS. (C) 2001 Elsevier Science B.V . All rights reserved.