Interferon-Gamma-Dependent/Independent Expression of Indoleamine 2,3-Dioxygenase

Takikawa, Osamu; Tagawa, Yoshitsugu; Iwakura, Yoichiro; Yoshida, Ryotaro; Truscott, Roger J.W.

doi:10.1007/978-1-4615-4709-9_68

Cited by 85 publications

(70 citation statements)

References 17 publications

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“…Intraperitoneal administration of BCG to mice is rapidly followed by long-lasting mycobacterial dissemination in all organs (particularly the lungs) except the brain (Tsenova et al, 1999) and by a drastic increase in circulating IFN-γ (Sander et al, 1995), a key cytokine for the activation of IDO (Takikawa et al, 1999). We first demonstrated that BCG inoculation causes a persistent activation of peripheral and brain IDO in mice for up to 3 weeks, resulting in decreased TRP levels (Moreau et al, 2005).…”

Section: Introductionmentioning

confidence: 70%

“…Since KYN is the major product of TRP degradation (Dale et al, 2000), these results can be explained by an enhanced activation of the TRP-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) (Wirleitner et al, 2003). This extrahepatic enzyme is activated in monocytes, macrophages and brain microglia in response to proinflammatory cytokines, mainly interferon-gamma (IFN-γ) and tumor necrosis factoralpha (TNF-α) (Fujigaki et al, 2006;Takikawa et al, 1999). In cancer patients treated by cytokine immunotherapy, the fall in plasma levels of TRP is correlated with the intensity of depressive symptoms (Capuron et al, 2002b), indicating that IDO activation might play a role in cytokine-induced depressive symptoms (Dantzer et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Moreau

André

O’Connor

et al. 2008

Brain, Behavior, and Immunity

143

151

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Although cytokine-induced sickness behavior is now well-established, the mechanisms by which chronic inflammation and depression are linked still remain elusive. Therefore this study aimed to develop a suitable model to identify the neurobiological basis of depressive-like behavior induced by chronic inflammation, independently of sickness behavior. We chose to measure the behavioral consequences of chronic inoculation of mice with Bacillus Calmette-Guerin (BCG), which has been shown to chronically activate both lung and brain indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme that mediates the occurrence of depressive-like behavior following acute innate immune system activation. BCG inoculation induced an acute episode of sickness (approximately 5 days) that was followed by development of delayed depressive-like behaviors lasting over several weeks. Transient body weight loss, reduction of motor activity and the febrile response to BCG were dissociated temporarily from a sustained increase in the duration of immobility in both forced swim and tail suspension tests, reduced voluntary wheel running and decreased preference for sucrose (a test of anhedonia). Moreover, we show that a distinct pattern of cytokine production and IDO activation parallels the transition from sickness to depression. Protracted depressive-like behavior, but not sickness behavior, was associated with sustained increase in plasma interferon-γ and TNF-α concentrations and peripheral IDO activation. Together, these promising new data establish BCG inoculation of mice as a reliable rodent model of chronic inflammation-induced depressive-like behaviors that recapitulate many clinical observations and provide important clues about the neurobiological basis through which cytokines may have an impact on affective behaviors.

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Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Moreau

André

O’Connor

et al. 2008

Brain, Behavior, and Immunity

143

151

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“…IFN-g and TNF-a are the main inducers of IDO activation. 5,6 Minocycline has already been shown to block IFN-g-mediated protein kinase C (a/bII) phosphorylation and nuclear translocation of both protein kinase C (a/bII) and IRF-1, 17 which is necessary for IDO activation. It also inhibits nuclear factor k-B and MAP kinase activation, 35 which are both necessary for the synergistic effects of TNF-a and IFN-g on IDO activation.…”

Section: Discussionmentioning

confidence: 99%

“…4 IDO is an extrahepatic enzyme that is present in macrophages and other cells that degrades the essential amino acid tryptophan along the kynurenine pathway. This enzyme is induced by proinflammatory cytokines, mainly interferon-g (IFN-g) 5 and tumor-necrosis factor-a (TNF-a). 6,7 When IDO is activated in conditions of chronic inflammation, its degree of activation is correlated to the intensity of depressive symptoms, as observed in cancer patients chronically treated with IFN-a.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O’Connor

Lawson²,

André³

et al. 2008

Mol Psychiatry

1,126

992

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Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.

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“…Kynurenine metabolites: Quinolinic acid (QUIN) is an NMDA receptor agonist and a metabolite of the kynurenine pathway of tryptophan degradation, regulated in part by PICs through activation of IDO [71,72].…”

Section: Effects On Glutamate Neurotransmissionmentioning

confidence: 99%

Sick and Tired: Mood, Fatigue, and Inflammation in Cancer

Kruse

Strouse

2015

Curr Psychiatry Rep

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Cancer patients commonly experience depression and fatigue before, during, and after treatment. Symptoms can be debilitating, and the risks associated with unrecognized or inadequately treated depression are substantial. Inflammation may be important in the genesis of depression and fatigue in cancer patients; potential neurobiological mechanisms of inflammation-related behavioral symptoms are reviewed. Randomized studies of pharmacologic treatments for depression in cancer populations are limited, but available data are generally encouraging. Studies of pharmacologic treatments for cancer-related fatigue have been more numerous but with mixed results. A practical approach to pharmacologic treatment of depression and fatigue in cancer patients involves weighing the potential risks and benefits of specific agents, including potential for adverse or advantageous side effects. Progress in understanding the neurobiological mechanisms underlying inflammation-related behavioral symptoms will provide opportunities for the development of novel and targeted treatments.

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Interferon-Gamma-Dependent/Independent Expression of Indoleamine 2,3-Dioxygenase

Cited by 85 publications

References 17 publications

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

Sick and Tired: Mood, Fatigue, and Inflammation in Cancer

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