Male adolescent rats display blunted cytokine responses in the CNS after acute ethanol or lipopolysaccharide exposure

PHYSIOLOGY & BEHAVIOR

卷:148

Article

Doremus-Fitzwater, Tamara L.¹  Gano, Anny¹  Paniccia, Jacqueline E.¹  Deak, Terrence¹ 

[1] SUNY Binghamton, Dept Psychol, Behav Neurosci Program, DEARC, Binghamton, NY 13902 USA

关键词: Rat;    Adolescent;    Ethanol;    Lipopolysaccharide;    Cytokines;    Endotoxin;   

DOI  :  10.1016/j.physbeh.2015.02.032

来源: Elsevier

【 摘 要 】

Alcohol induces widespread changes in cytokine expression, with recent data from our laboratory having demonstrated that, during acute ethanol intoxication, adult rats exhibit consistent increases in interleukin (IL)-6 mRNA expression in several brain regions, while showing reductions in IL-1 and TNF alpha expression. Given evidence indicating that adolescence may be an ontogenetic period in which some neuroimmune processes and cells may not yet have fully matured, the purpose of the current experiments was to examine potential age differences in the central cytokine response of adolescent.(P31-33 days of age) and adult (69-71 days of age) rats to either an acute immune (lipopolysaccharide; LPS) or non-immune challenge (ethanol). In Experiment 1, male Sprague-Dawley rats were given an intraperitoneal (i.p.) injection of either sterile saline, LPS (250 mu g/kg), or ethanol (4-g/kg), and then trunk blood and brain tissue were collected 3 h later for measurement of blood ethanol concentrations (BECs), plasma endotoxin, and central mRNA expression of several immune-related gene targets. In Experiment 2, the response to intragastrically (Lg.) administered ethanol was examined and compared to animals given tap water (i.g.). Results showed that LPS stimulated robust increases in expression of IL-1, IL-6, TNF alpha, and I kappa B alpha in the hippocampus, PVN, and amygdala, and that thee increases were generally less pronounced in adolescents relative to adults. Following an i.p. ethanol challenge, IL-6 and I kappa B alpha expression was significantly increased in both ages in the PVN and amygdala, and adults exhibited even greater increases in I kappa B alpha than adolescents. Lg. administration of ethanol also increased IL-6 and I kappa B alpha expression in all three brain regions, with hippocampal IL-6 elevated even more so in adults compared to adolescents. Furthermore, assessment of plasma endotoxin concentrations revealed (i) whereas robust increases in plasma endotoxin were observed in adults injected with LPS, no corresponding elevations were seen in adolescents after LPS; and (ii) neither adolescents nor adults demonstrated increases in plasma endotoxin concentrations following i.p. or i.g. ethanol administration. Analysis of BECs indicated that, for both routes of exposure, adolescents exhibited lower BECs than adults. Taken together, these data suggest that categorically different mechanisms are involved in the central cytokine response to antigen exposure versus ethanol administration. Furthermore, these findings confirm once again that acute ethanol intoxication is a potent activator of brain cytokine, and calls for future studies to identify the mechanisms underlying age-related differences in the cytokine response observed during ethanol intoxication. (C) 2015 Elsevier Inc All rights reserved.

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