Transcriptional Activation of Indoleamine Dioxygenase by Interleukin 1 and Tumor Necrosis Factor Α in Interferon-Treated Epithelial Cells

Babcock, Tricia A.; Carlin, Joseph M.

doi:10.1006/cyto.1999.0661

Cited by 150 publications

(119 citation statements)

References 24 publications

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“…94 Cytokines may also induce depressive symptoms by affecting the serotonergic system. In fact, some cytokines, such as IFN-g, IFN-a, TNF-a and IL-1, have all been shown to upregulate the enzyme indoleamine 2,3-dioxygenase (IDO) expression [95][96][97][98] and, thus, cause increased metabolism of tryptophan, resulting in decreased availability of tryptophan to synthesize 5-HT. It has also been shown that patients treated with cytokines had decreased blood levels of tryptophan 99 and therefore it is very likely that cytokines can suppress serotonin by activating IDO that catabolizes tryptophan.…”

Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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Although poststroke depression is unlikely to represent a single disorder and numerous etiologies for different kinds of poststroke depression will likely emerge as the result of future research, we believe that a number of poststroke depressive disorders are likely to be the result of specific changes in brain pathology and neurophysiology. Nevertheless, there are relatively few hypotheses about the pathophysiology of poststroke depression. This paper, therefore, proposes a new hypothesis for poststroke depression involving increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas linked to the pathogenesis of mood disorders. This paper reviews the evidence supporting the hypothesis that proinflammatory cytokines are involved in the occurrence of stroke as well as mood disorders linked to the brain damage. The increased production of proinflammatory cytokines such as IL-1b, TNF-a or IL-18 resulting from stroke may lead to an amplification of the inflammatory process, particularly in limbic areas, and widespread activation of indoleamine 2,3-dioxygenase (IDO) and subsequently to depletion of serotonin in paralimbic regions such as the ventral lateral frontal cortex, polar temporal cortex and basal ganglia. The resultant physiological dysfunction may lead to poststroke depression. Future investigations may explore this hypothesis through more extensive studies on the role of proinflammatory cytokines, such as IL-1b, TNF-a or even IL-18, in patients with poststroke depression. Molecular Psychiatry (2006) 11, 984-991.

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Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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“…21 Numerous studies have shown that this compound, being an end product of tryptophan degradation along the kynurenine pathway, may serve as a marker of immunoactivation. 7 Thus, several cytokines are able to induce or repress critical enzymes of the kynurenine pathway like indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), 22,23 leading to increased KYNA production. Kynurenic acid is an antagonist at the glycine site of the N-methyl-D-aspartate receptor 24,25 as well as at the cholinergic α7* nicotinic receptor, 26 and hence provides a potential link between the immune system and glutamatergic/ cholinergic neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Söderlund

Olsson

Samuelsson

et al. 2011

J Psychiatry Neurosci

168

121

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Background:In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention.Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its pathophysiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed. Methods: We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar dis order type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system. Results: The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respect ively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10). Limitations: All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out. Conclusion: Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder. In recent years, a role of the immune system in the pathogenesis of psychiatric diseases has gained increased attention. In this regard, many investigators have focused on cytokines, proteins that directly initiate and control immunological responses. We recently demonstrated a selective activation of brain interleukin (IL)-1β in schizophrenia, 2 a disease that appears similar to bipolar disorder with regard to symptomatology, treatment and risk genes. 3,4 Interestingly, a polymorphism in the promoter region of the IL1B gene has been suggested to comprise a shared genetic susceptibility for bipolar disorder and schizophrenia. 5 Indeed, bipolar disorder appears to be linked to inflammation, as indicated by genetic polymorphisms, gene expression and cytokine activation, 6 although direct evidence for a pathophysiological involvement of the immune system of the brain is still sparse. This may be 115 related to the fact that evaluation of cytokine levels in patients with bipolar disorder has been restricted to serum analyses. The bidirectional communication between the immune system of the brain and that of peripheral organs is complex, 7 and serum cytokines do not predict brain cytokine activation in healthy volunteers. 8 Hence, the immune system of the brain, including local cytokine release from microglia and astrocytes, may be independent of the immune sys...

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“…2). Proinflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin (IL)-1, IL-2, and IFN-g affect serotonin metabolism by stimulating or enhancing the stimulation of IDO, which leads to a peripheral depletion of tryptophan, which, in turn, leads to depletion of 5-HTP and serotonin (Carlin et al, 1989;Babcock & Carlin, 2000;Fig. 2).…”

Section: Factors Affecting 5-hydroxytryptophan Availability For Serotmentioning

confidence: 99%

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Turner

Loftis

Blackwell

2006

Pharmacology & Therapeutics

274

158

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This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome. D

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Transcriptional Activation of Indoleamine Dioxygenase by Interleukin 1 and Tumor Necrosis Factor Α in Interferon-Treated Epithelial Cells

Cited by 150 publications

References 24 publications

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

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