title: Intoxication- and withdrawal-dependent expression of central and peripheral cytokines following initial ethanol exposure.
abstract: BACKGROUND
  Evidence has emerged demonstrating that ethanol (EtOH) influences cytokine expression within the central nervous system, although most studies have examined long-term exposure. Thus, the cytokine response to an acute EtOH challenge was investigated, in order to characterize profiles of cytokine changes following acute exposure.
  
  
  METHODS
  Rats pups were injected intraperitoneally (i.p.) with 2-g/kg EtOH, and IL-1 mRNA and protein were assessed 0, 60, 120, 180, and 240 minutes post injection (Experiment 1). In Experiments 2 to 5, the expression of several cytokines was examined in adult male rats during acute intoxication (3 hours after 4-g/kg EtOH), as well as withdrawal (18 hours post injection), after i.p. or intragastric (i.g.) EtOH administration.
  
  
  RESULTS
  Early in ontogeny, acute EtOH significantly decreased brain IL-1 mRNA and protein. Subsequently, when adult rats were examined, significant and temporally dynamic alterations in central and peripheral cytokines were observed following acute i.p. EtOH exposure (4 g/kg). Although cytokine- and region-dependent central IL-6 expression was generally increased and tumor necrosis factor alpha decreased during intoxication, IL-1 expression exhibited increases during withdrawal. In the periphery, acute i.p. EtOH elevated expression of all cytokines, with the response growing in magnitude as the time post injection increased. Following acute i.g. EtOH (4 g/kg), intoxication-related increases in IL-6 expression were again observed in the paraventricular nucleus of the hypothalamus (PVN), although to a lesser extent. Long-term, voluntary, intermittent EtOH consumption resulted in tolerance to the effects of an i.g. EtOH challenge (4 g/kg) on PVN IL-6 expression, whereas these same elevations in IL-6 expression were still seen in the amygdala in rats with a history of moderate EtOH intake. Treatment with minocycline did not significantly attenuate i.p. or i.g. EtOH-induced changes in central cytokine expression.
  
  
  CONCLUSIONS
  Together, these studies provide a foundation for understanding fluctuations in central and peripheral cytokines following acute EtOH as potential contributors to the constellation of neural and behavioral alterations observed during EtOH intoxication and withdrawal.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, Binghamton University-State University of New York, Binghamton, New York.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Doremus-Fitzwater
authors.forename: Hollin M
authors.initials: HM
authors.lastname: Buck
authors.forename: Kelly
authors.initials: K
authors.lastname: Bordner
authors.forename: Laura
authors.initials: L
authors.lastname: Richey
authors.forename: Megan E
authors.initials: ME
authors.lastname: Jones
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
mesh_terms: D000367:Age Factors; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004361:Drug Tolerance; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D051381:Rats; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D008911:Minocycline; D003345:Corticosterone
keywords: Brain; Cytokine; Ethanol; Minocycline; Rat