TY - JOUR
T1 - Alcoholism and inflammation
T2 - Neuroimmunology of behavioral and mood disorders
AU - Kelley, Keith W.
AU - Dantzer, Robert
N1 - Funding Information:
The authors have no conflicting financial interests. Supported by NIH Grants to KWK (R01 AG 029573) and RD (R01 MH 079829).
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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.
AB - 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.
KW - 2,3 Indoleamine 2
KW - 3 Dioxygenase
KW - Alcoholism
KW - Depressive-like behavior
KW - Kynurenine
KW - Pro-inflammatory cytokines
KW - Sickness behavior
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U2 - 10.1016/j.bbi.2010.12.013
DO - 10.1016/j.bbi.2010.12.013
M3 - Review article
C2 - 21193024
AN - SCOPUS:79955717804
SN - 0889-1591
VL - 25
SP - S13-S20
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
IS - SUPPL. 1
ER -