| Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders. | |
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MedLine Citation:
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PMID: 21193024 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alcohol abuse changes behavior and can induce major mood disorders such as depression. Recent evidence in pre-clinical rodent models and humans now supports the conclusion that the innate immune system is an important physiological link between alcoholism and major depressive disorders. Deficiency of toll-like receptor 4 (TLR4), a protein that has been known to immunologists for 50 years, not only prevents lipopolysaccharide (LPS)-induced sickness behavior but recently has been demonstrated to induce resistance to chronic alcohol ingestion. Activation of the immune system by acute administration of LPS, a TLR4 agonist, as well as chronic infection with Bacille Calmette-Guérin (BCG), causes development of depressive-like behaviors in pre-clinical rodent models. Induction of an enzyme expressed primarily in macrophages and microglia, 2,3 indoleamine dioxygenase, shunts tryptophan catabolism to form kynurenine metabolites. This enzyme is both necessary and sufficient for expression of LPS and BCG-induced depressive-like behaviors in mice. New findings have extended these concepts to humans by showing that tryptophan catabolites of 2,3 indoleamine dioxygenase are elevated in the cerebrospinal fluid of hepatitis patients treated with the recombinant cytokine interferon-α. The remarkable conservation from mice to humans of the impact of inflammation on mood emphasizes the ever-expanding role for cross-talk among diverse physiological symptoms that are likely to be involved in the pathogenesis of alcohol abuse. These findings present new and challenging opportunities for scientists who are engaged in brain, behavior and immunity research. |
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Authors:
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Keith W Kelley; Robert Dantzer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2010-12-28 |
Journal Detail:
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Title: Brain, behavior, and immunity Volume: 25 Suppl 1 ISSN: 1090-2139 ISO Abbreviation: Brain Behav. Immun. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-08-08 Revised Date: 2011-09-22 |
Medline Journal Info:
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Nlm Unique ID: 8800478 Medline TA: Brain Behav Immun Country: United States |
Other Details:
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Languages: eng Pagination: S13-20 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Integrative Immunology and Behavior Program, Department of Animal Sciences, College of ACES, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. kwkelley@illinois.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcoholism
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immunology* Animals Behavior, Animal Disease Models, Animal Inflammation / immunology* Mice Mood Disorders / immunology* Neuroimmunomodulation / immunology* Toll-Like Receptor 4 / immunology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AG 029573/AG/NIA NIH HHS; R01 AG029573-04/AG/NIA NIH HHS; R01 AG029573-04S1/AG/NIA NIH HHS; R01 MH 079829/MH/NIMH NIH HHS; R01 MH079829-05/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Toll-Like Receptor 4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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