In vivo neutralization of endogenous brain fractalkine increases hippocampal TNFalpha 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 inflammatory responses. In this study, we have investigated the in vivo anti-inflammatory potential of fractalkine in a model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS) in rats. LPS induces a rapid and acute production of the pro-inflammatory cytokine, TNFalpha, in hippocampus and cerebrospinal fluid (CSF), and an increase of 8-isoprostane levels, a marker of oxidative stress, in hippocampus. Although intracerebroventricular injection of fractalkine has no effect on TNFalpha 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.
Zujovic
V
V
Sanofi-Synthélabo, CNS Research Department, 31 Avenue Paul Vaillant-Couturier, 92225 Cedex, Bagneux, France.
Schussler
N
N
Jourdain
D
D
Duverger
D
D
Taupin
V
V
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D028441:F2-Isoprostanes; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism*
D000906:Antibodies; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515540:Cx3cl1 protein, rat; D028441:F2-Isoprostanes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost