title: Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1 beta in male rats.
abstract: BACKGROUND
  Chronic and acute alcohol use exert profound modulatory effects on the immune system which manifest as impaired host defense against infections. An important feature of this response is the interaction between the immune and the central nervous systems. This study investigated the effects of 14 days of alcohol exposure on cytokine-mediated neuroimmune interactions that affect the febrile component of the host-defense response.
  
  
  METHODS
  Adult male rats were fed a liquid diet containing ethanol (EtOH, 5% w/v) for 14 days. Pair-fed and normal chow- and water-fed rats served as controls. Continuous biotelemetric recordings of body temperature and locomotor activity commencing after 14 days of EtOH feeding were used to determine the effects of chronic EtOH on the circadian pattern of temperature and activity, on the febrile response to intraperitoneal (ip) administration of lipopolysaccharide (LPS) and interleukin (IL)-1beta, and on fever induced by IL-1beta administered intracerebroventricularly. We also examined the effects of EtOH consumption on LPS-induced hypothalamic production of the pyrogenic cytokines IL-1beta and tumor necrosis factor-alpha (TNFalpha) and on the blood levels of IL-1beta, TNFalpha, IL-6, adrenocorticotropin, and corticosterone at 2, 4, and 6 hr after ip LPS.
  
  
  RESULTS
  Fourteen days of EtOH consumption blunted the circadian increases in temperature and activity that normally occur in the dark phase of the light/dark cycle without affecting light-phase temperature or activity. EtOH consumption attenuated fever induced by LPS or IL-1beta administered ip during the light phase and significantly reduced hypothalamic production of IL-1beta. LPS-induced increases in hypothalamic TNFalpha and blood cytokines, adrenocorticotropin, and corticosterone were unaffected. Central administration of IL-1beta produced a normal febrile response in chronic-EtOH rats.
  
  
  CONCLUSIONS
  The attenuated LPS- and IL-1beta-induced febrile responses in EtOH-consuming rats and the corresponding deficit in hypothalamic production of IL-1beta suggest that alcohol may impair IL-1beta-mediated neuroimmune communication.
authors.affiliation: Department of Neurobiology and Brain Research Institute, University of California-Los Angeles School of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, 90095-1763, USA. ataylor@mednet.ucla.edu
authors.forename: Anna N
authors.initials: AN
authors.lastname: Taylor
authors.forename: Delia L
authors.initials: DL
authors.lastname: Tio
authors.forename: Ngy S
authors.initials: NS
authors.lastname: Heng
authors.forename: Raz
authors.initials: R
authors.lastname: Yirmiya
mesh_terms: D000428:Alcohol Drinking / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000276:immunology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000276:immunology; D000431:Ethanol / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced* / Q000276:immunology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D007375:Interleukin-1; D008070:Lipopolysaccharides; D000431:Ethanol