Ethanol suppression of the hypothalamic proopiomelanocortin level and the splenic NK cell cytolytic activity is associated with a reduction in the expression of proinflammatory cytokines but not anti-inflammatory cytokines in neuroendocrine and immune cells

Cui Ping Chen, Nadka I. Boyadjieva, Juan P. Advis, Dipak K. Sarkar

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Immune signals activate a network of cytokines in the central nervous system (CNS) that in turn causes release of neurotransmitters and hormones to modulate immune cell functions. We have recently shown that hypothalamic β-endorphin neurons, via inhibition of the sympathetic neuronal activity, activate natural killer (NK) cell function in the spleen, and this communication is disrupted following chronic ethanol administration. β-Endorphin neuronal function is known to be regulated by various proinflammatory and anti-inflammatory cytokines. The effects of ethanol on the proinflammatory and anti-inflammatory cytokines known to control β-endorphin neuronal and NK cell functions during immune challenges have not been determined. Methods: In the present study, we evaluated the effects of chronic ethanol consumption on the basal and lipopolysaccharide (LPS)-activated NK cells' functions in the spleen, the β-endorphin peptide precursor proopiomelanocortin (POMC) gene expression in the arcuate nucleus (ARC) of the hypothalamus, and mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and anti-inflammatory cytokines IL-6 and IL-10 in the spleen and in the ARC. Male rats were ad libitum fed rat chow (ad lib-fed), pair-fed an isocaloric liquid diet, or fed an ethanol-containing liquid diet, and each was treated with LPS (100 μg/kg body weight). After 2 hours, splenocytes and ARC tissues were isolated and used for this study. Splenocytes were used to determine mRNA levels of IL-1β, TNF-α, IL-6, IL-10, granzyme B, and perforin using the real-time RT-PCR assays. Splenocytes were also used to determine the cytolytic activity using a standard 4-hour 51Cr release assay against YAC-1 lymphoma target cells. Arcuate nuclei were used to determine IL-1β, TNF-α, IL-6, IL-10, and POMC mRNA levels using real-time RT-PCR assays. Results: The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS-stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS-induced levels of IL-1β and TNF-α mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.

Original languageEnglish (US)
Pages (from-to)1925-1932
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2006

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Neuroendocrine Cells
Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
Natural Killer Cells
Anti-Inflammatory Agents
Ethanol
Cytokines
Endorphins
Lipopolysaccharides
Messenger RNA
Spleen
Interleukin-6
Interleukin-1
Interleukin-10
Nutrition
Assays
Diet
Rats
Real-Time Polymerase Chain Reaction
Liquids

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Medicine (miscellaneous)
  • Toxicology

Keywords

  • Arcuate Nuclei
  • Cytokines
  • Ethanol
  • Granzyme B
  • NK Cell Cytolytic Activity
  • Perforin
  • Proopiomelanocortin
  • Rats
  • Spleen

Cite this

@article{35843bdf6c364d6b8f569f3daaf177fb,
title = "Ethanol suppression of the hypothalamic proopiomelanocortin level and the splenic NK cell cytolytic activity is associated with a reduction in the expression of proinflammatory cytokines but not anti-inflammatory cytokines in neuroendocrine and immune cells",
abstract = "Background: Immune signals activate a network of cytokines in the central nervous system (CNS) that in turn causes release of neurotransmitters and hormones to modulate immune cell functions. We have recently shown that hypothalamic β-endorphin neurons, via inhibition of the sympathetic neuronal activity, activate natural killer (NK) cell function in the spleen, and this communication is disrupted following chronic ethanol administration. β-Endorphin neuronal function is known to be regulated by various proinflammatory and anti-inflammatory cytokines. The effects of ethanol on the proinflammatory and anti-inflammatory cytokines known to control β-endorphin neuronal and NK cell functions during immune challenges have not been determined. Methods: In the present study, we evaluated the effects of chronic ethanol consumption on the basal and lipopolysaccharide (LPS)-activated NK cells' functions in the spleen, the β-endorphin peptide precursor proopiomelanocortin (POMC) gene expression in the arcuate nucleus (ARC) of the hypothalamus, and mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and anti-inflammatory cytokines IL-6 and IL-10 in the spleen and in the ARC. Male rats were ad libitum fed rat chow (ad lib-fed), pair-fed an isocaloric liquid diet, or fed an ethanol-containing liquid diet, and each was treated with LPS (100 μg/kg body weight). After 2 hours, splenocytes and ARC tissues were isolated and used for this study. Splenocytes were used to determine mRNA levels of IL-1β, TNF-α, IL-6, IL-10, granzyme B, and perforin using the real-time RT-PCR assays. Splenocytes were also used to determine the cytolytic activity using a standard 4-hour 51Cr release assay against YAC-1 lymphoma target cells. Arcuate nuclei were used to determine IL-1β, TNF-α, IL-6, IL-10, and POMC mRNA levels using real-time RT-PCR assays. Results: The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS-stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS-induced levels of IL-1β and TNF-α mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.",
keywords = "Arcuate Nuclei, Cytokines, Ethanol, Granzyme B, NK Cell Cytolytic Activity, Perforin, Proopiomelanocortin, Rats, Spleen",
author = "Chen, {Cui Ping} and Boyadjieva, {Nadka I.} and Advis, {Juan P.} and Sarkar, {Dipak K.}",
year = "2006",
month = "11",
day = "1",
doi = "https://doi.org/10.1111/j.1530-0277.2006.00237.x",
language = "English (US)",
volume = "30",
pages = "1925--1932",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
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}

TY - JOUR

T1 - Ethanol suppression of the hypothalamic proopiomelanocortin level and the splenic NK cell cytolytic activity is associated with a reduction in the expression of proinflammatory cytokines but not anti-inflammatory cytokines in neuroendocrine and immune cells

AU - Chen, Cui Ping

AU - Boyadjieva, Nadka I.

AU - Advis, Juan P.

AU - Sarkar, Dipak K.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Background: Immune signals activate a network of cytokines in the central nervous system (CNS) that in turn causes release of neurotransmitters and hormones to modulate immune cell functions. We have recently shown that hypothalamic β-endorphin neurons, via inhibition of the sympathetic neuronal activity, activate natural killer (NK) cell function in the spleen, and this communication is disrupted following chronic ethanol administration. β-Endorphin neuronal function is known to be regulated by various proinflammatory and anti-inflammatory cytokines. The effects of ethanol on the proinflammatory and anti-inflammatory cytokines known to control β-endorphin neuronal and NK cell functions during immune challenges have not been determined. Methods: In the present study, we evaluated the effects of chronic ethanol consumption on the basal and lipopolysaccharide (LPS)-activated NK cells' functions in the spleen, the β-endorphin peptide precursor proopiomelanocortin (POMC) gene expression in the arcuate nucleus (ARC) of the hypothalamus, and mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and anti-inflammatory cytokines IL-6 and IL-10 in the spleen and in the ARC. Male rats were ad libitum fed rat chow (ad lib-fed), pair-fed an isocaloric liquid diet, or fed an ethanol-containing liquid diet, and each was treated with LPS (100 μg/kg body weight). After 2 hours, splenocytes and ARC tissues were isolated and used for this study. Splenocytes were used to determine mRNA levels of IL-1β, TNF-α, IL-6, IL-10, granzyme B, and perforin using the real-time RT-PCR assays. Splenocytes were also used to determine the cytolytic activity using a standard 4-hour 51Cr release assay against YAC-1 lymphoma target cells. Arcuate nuclei were used to determine IL-1β, TNF-α, IL-6, IL-10, and POMC mRNA levels using real-time RT-PCR assays. Results: The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS-stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS-induced levels of IL-1β and TNF-α mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.

AB - Background: Immune signals activate a network of cytokines in the central nervous system (CNS) that in turn causes release of neurotransmitters and hormones to modulate immune cell functions. We have recently shown that hypothalamic β-endorphin neurons, via inhibition of the sympathetic neuronal activity, activate natural killer (NK) cell function in the spleen, and this communication is disrupted following chronic ethanol administration. β-Endorphin neuronal function is known to be regulated by various proinflammatory and anti-inflammatory cytokines. The effects of ethanol on the proinflammatory and anti-inflammatory cytokines known to control β-endorphin neuronal and NK cell functions during immune challenges have not been determined. Methods: In the present study, we evaluated the effects of chronic ethanol consumption on the basal and lipopolysaccharide (LPS)-activated NK cells' functions in the spleen, the β-endorphin peptide precursor proopiomelanocortin (POMC) gene expression in the arcuate nucleus (ARC) of the hypothalamus, and mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and anti-inflammatory cytokines IL-6 and IL-10 in the spleen and in the ARC. Male rats were ad libitum fed rat chow (ad lib-fed), pair-fed an isocaloric liquid diet, or fed an ethanol-containing liquid diet, and each was treated with LPS (100 μg/kg body weight). After 2 hours, splenocytes and ARC tissues were isolated and used for this study. Splenocytes were used to determine mRNA levels of IL-1β, TNF-α, IL-6, IL-10, granzyme B, and perforin using the real-time RT-PCR assays. Splenocytes were also used to determine the cytolytic activity using a standard 4-hour 51Cr release assay against YAC-1 lymphoma target cells. Arcuate nuclei were used to determine IL-1β, TNF-α, IL-6, IL-10, and POMC mRNA levels using real-time RT-PCR assays. Results: The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS-stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS-induced levels of IL-1β and TNF-α mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.

KW - Arcuate Nuclei

KW - Cytokines

KW - Ethanol

KW - Granzyme B

KW - NK Cell Cytolytic Activity

KW - Perforin

KW - Proopiomelanocortin

KW - Rats

KW - Spleen

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U2 - https://doi.org/10.1111/j.1530-0277.2006.00237.x

DO - https://doi.org/10.1111/j.1530-0277.2006.00237.x

M3 - Article

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VL - 30

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EP - 1932

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

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ER -