A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques

Alcohol Clin Exp Res. 2012 Jun;36(6):995-1003. doi: 10.1111/j.1530-0277.2011.01685.x. Epub 2011 Dec 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / drug effects*
  • Alcohol Drinking / adverse effects*
  • Animals
  • Central Nervous System Depressants / pharmacology*
  • Cytokines / blood
  • Cytokines / drug effects
  • Ethanol / pharmacology*
  • Hydrocortisone / blood*
  • Janus Kinases / blood
  • Janus Kinases / drug effects*
  • Longitudinal Studies
  • Macaca fascicularis
  • Male
  • Matrix Metalloproteinases, Secreted / blood
  • Matrix Metalloproteinases, Secreted / drug effects
  • NF-kappa B / blood
  • NF-kappa B / drug effects*
  • Self Administration

Substances

  • Central Nervous System Depressants
  • Cytokines
  • NF-kappa B
  • Ethanol
  • Adrenocorticotropic Hormone
  • Janus Kinases
  • Matrix Metalloproteinases, Secreted
  • Hydrocortisone