title: A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques.
abstract: BACKGROUND
  Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates.
  
  
  METHODS
  Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months, and after 12 months of 22-hour daily concurrent access to ethanol and water.
  
  
  RESULTS
  Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates.
  
  
  CONCLUSIONS
  Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006-3448, USA. helmsc@ohsu.edu
authors.forename: Christa M
authors.initials: CM
authors.lastname: Helms
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Sophia
authors.initials: S
authors.lastname: Jeng
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
authors.forename: Kent E
authors.initials: KE
authors.lastname: Vrana
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood*; D053612:Janus Kinases / Q000097:blood / Q000187:drug effects*; D008137:Longitudinal Studies; D008252:Macaca fascicularis; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000097:blood / Q000187:drug effects; D016328:NF-kappa B / Q000097:blood / Q000187:drug effects*; D012646:Self Administration
chemical_list: D002492:Central Nervous System Depressants; D016207:Cytokines; D016328:NF-kappa B; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D053612:Janus Kinases; D053505:Matrix Metalloproteinases, Secreted; D006854:Hydrocortisone