Plasma Concentrations of Interleukin-1β, Interleukin-6, Soluble Interleukin-2 Receptor and Tumor Necrosis Factor α of Depressed Patients in Japan

Kagaya, Ariyuki; Kugaya, Akira; Takebayashi, Minoru; Fukue-Saeki, Mayumi; Saeki, Toshinari; Yamawaki, Shigeto; Uchitomi, Yosuke

doi:10.1159/000054867

Cited by 91 publications

(45 citation statements)

References 19 publications

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“…106 Contradictory results are very few indicating reduced, 107 or not altered, serum IL-6 levels. 97,108,109 The potential influence of possibly interfering variables, such as age, smoking, gender, recent infections and prior medication (including insufficient washout period) to IL-6 release and concentration must be considered. 110 An agerelated increase of IL-6 serum values was reported in patients with MD, 111 but also elderly depressed patients exhibit higher IL-6 serum levels compared with control persons of comparable age.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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“…Indeed, treatment with SSRIs has been shown to decrease MD associated cytokine elevations. In particular, the levels of inflammatory cytokines IL-1β, IL-6 and TNFα have been reported to be reduced following SSRI treatment (Basterzi et al, 2005;Kagaya et al, 2001;Lanquillon et al, 2000;Leo et al, 2006;Tuglu et al, 2003;Yoshimura et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

“…Indeed, though many studies showed that antidepressants have anti-inflammatory effects (Basterzi et al, 2005;Kagaya et al, 2001;Lanquillon et al, 2000;Leo et al, 2006;Tuglu et al, 2003;Yoshimura et al, 2009), an increasing number of studies are reporting a proinflammatory action (Chen et al, 2010;Haastrup et al, 2012;Hannestad et al, 2011;Jazayeri et al, 2010;Kim et al, 2013;Song et al, 2009). In addition, the bi-directional crosstalk between SSRI administration and inflammation has been described also by studies investigating the effects of antiinflammatory drugs on antidepressant efficacy.…”

mentioning

confidence: 99%

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Alboni

Poggini

Garofalo

et al. 2016

Brain, Behavior, and Immunity

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It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti-or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti-and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions. AbstractIt has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these drugs act either as anti-or proinflammatory. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21 days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti-and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that...

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“…Furthermore, cerebrospinal IL-1beta levels were correlated with the severity of depression (Levine et al, 1999), age of onset (Anisman et al, 1999), and duration of illness (Anisman et al, 1999). However, several studies have found that the IL1beta levels were unchanged in MDD patients (Rothermundt et al, 2001;Kagaya et al, 2001;Brambilla and Maggioni, 1998) and were not correlated with the severity of depression (Rothermundt et al, 2001). Furthermore, Weizman et al (1994) found a significant reduction in IL-1beta production in untreated MDD patients compared to normal controls and a significant increase of IL-1beta synthesis after drug treatment.…”

Section: Introductionmentioning

confidence: 99%

Association Study of the Interleukin-1beta (C-511T) Genetic Polymorphism with Major Depressive Disorder, Associated Symptomatology, and Antidepressant Response

Yu¹,

Chen

Hong

et al. 2003

Neuropsychopharmacol

135

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Proinflammatory cytokines, including interleukin (IL)-1beta, are suggested to have a role in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied biallelic polymorphism in the promoter region (position -511) of the IL-1beta gene in 157 patients with MDD and in 112 controls. We also examined the association of this polymorphism and fluoxetine therapeutic response in 119 MDD patients who received a 4-week fluoxetine treatment. No significant difference was found in the genetic polymorphism between MDD patients and controls. However, MDD patients who were homozygous for the -511T allele of the IL-1beta gene had a trend of less severity of depressive symptoms and more favorable fluoxetine therapeutic response than -511C carriers. Further study with a larger sample is needed to clarify the role of the IL-1beta genetic polymorphisms in the symptoms and treatment effects in MDD.

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Plasma Concentrations of Interleukin-1β, Interleukin-6, Soluble Interleukin-2 Receptor and Tumor Necrosis Factor α of Depressed Patients in Japan

Cited by 91 publications

References 19 publications

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Association Study of the Interleukin-1beta (C-511T) Genetic Polymorphism with Major Depressive Disorder, Associated Symptomatology, and Antidepressant Response

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