Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression

Maes, Michaël; Meltzer, Herbert Y.; Bosmans, Eugène; Bergmans, Raf; Vandoolaeghe, Eric; Ranjan, Rakesch; Desnyder, Roger

doi:10.1016/0165-0327(95)00028-l

Cited by 570 publications

(323 citation statements)

References 28 publications

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“…Because an acute phase response in the above conditions is probably driven by hypersecretion of pro-inflammatory cytokines (Maes et al 1993b), these in vivo data are in accordance with the contention that antidepressants have negative immunoregulatory effects in vitro and in vivo. Not all studies, however, were able to find that short-term treatment with fluoxetine significantly suppressed initially increased serum IL-6 and IL-2R concentrations in major depression (Maes et al 1995a). Finally, it is generally believed that tricyclic antidepressants have immunosuppressive effects ex vivo as well as in vivo (review : Miller and Lackner 1989).…”

Section: Discussionmentioning

confidence: 99%

Negative Immunoregulatory Effects of Antidepressants Inhibition of Interferon-γ and Stimulation of Interleukin-10 Secretion

Maes¹,

Song

Lin

et al. 1999

Neuropsychopharmacology

334

179

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Section: Discussionmentioning

confidence: 99%

Negative Immunoregulatory Effects of Antidepressants Inhibition of Interferon-γ and Stimulation of Interleukin-10 Secretion

Maes¹,

Song

Lin

et al. 1999

Neuropsychopharmacology

334

179

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“…Increased soluble IL-2-receptors (sIL-2R) levels reflect an increased production of IL-2. The blood levels of sIL-2R were repeatedly found to be higher in MD patients 65,66,87 as well as the in vitro production of IL-2. 88 According to the sickness behavior hypothesis, the cytokines TNF-a, IL-1 and IL-6 have frequently been investigated in MD.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 93%

“…199 However, there are again some conflicting results, showing no effect of certain antidepressants on serum levels of different cytokines. 65,100 Regarding the relationship between IL-6 and PGE 2 as mentioned above, an inhibiting action of antidepressants on PGE 2 would be expected. 200 Twenty years ago, it was suggested that antidepressants inhibit PGE 2 .…”

Section: Antidepressant Pharmacotherapymentioning

confidence: 98%

“…62,63 Activation of the immune system in MD The characteristics of the immune activation in MD include increased numbers of circulating lymphocytes and phagocytic cells, upregulated serum levels of parameters indicating activated immune cells (for example, soluble IL-2 receptor), higher serum concentrations of positive acute phase proteins (APP), coupled with reduced levels of negative APP, as well as an increased release of proinflammatory cytokines, such as IL-1, IL-2, TNF-a and IL-6 through activated macrophages and IFN-g through activated T cells. [64][65][66][67][68][69][70] Increased numbers of peripheral mononuclear cells have been described by different groups of researchers. [71][72][73] According to these findings, an increased secretion of neopterin has been described by several Immune-mediated alteration of serotonin and glutamate N Müller and MJ Schwarz groups of researchers.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

“…89 As a product of activated monocytes and macrophages, IL-6 is one of the most frequently investigated immune parameters in MD. The majority of reports demonstrate a markedly higher in vitro IL-6 production, 80,94 or higher serum IL-6 levels in depressed patients 65,87,93,[99][100][101][102][103][104] as well as IL-6 mRNA expression in leukocytes. 98 The elevation of IL-6 seems to be especially profound in the morning.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

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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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Immune Disturbances in Treatment-Resistant Depression: Modulation by Antidepressive Treatments

Maes

Vandoolaeghe

Hunsel

et al. 1997

Hum. Psychopharmacol. Clin. Exp.

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Recently, there were some reports that major depression is accompanied by significant alterations in the percentage and number of peripheral blood mononuclear cells (PBMCs), such as increased number of CD4+ T cells, B cells (e.g. CD19+, CD21+), number of leukocytes, monocytes and neutrophils and an increased CD4+/CD8+ T‐cell ratio. The aims of the present study were to examine the number and percentage of PBMCs in major and treatment‐resistant depressed (TRD) patients and the effects of antidepressant treatments on those PBMCs. Major depression was characterized by a significantly higher number of leukocytes and CD4+ T‐cells, a higher percentage of CD2+ T cells and CD4+ T cells, and a higher CD4+/CD8+ T‐cell ratio than normal controls. Patients with TRD had a significantly higher percentage of CD4+ T cells and CD4+/CD8+ T‐cell ratio, and a significantly lower percentage of CD8+ T cells than non‐TRD patients and normal controls. There were significant negative correlations between the length of the index episode or duration of illness and number or percentage of monocytes. Subchronic treatment with antidepressants significantly reduced the number of leukocytes and neutrophils, but had no effect either on the absolute number of the other PBMCs or on the CD4+/CD8+ T‐cell ratio. The results suggest that (i) the higher CD4+/CD8+ T‐cell ratio in major depression is a trait marker of that illness and of treatment resistance; (ii) the increased numbers of leukocytes and neutrophils are state markers of depression and are reduced by ‘subchronic’ antidepressant therapy; (iii) the number and percentage of monocytes decrease with respect to duration of illness and length of the index depressive episode. © 1997 by John Wiley & Sons, Ltd.

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Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression

Cited by 570 publications

References 28 publications

Negative Immunoregulatory Effects of Antidepressants Inhibition of Interferon-γ and Stimulation of Interleukin-10 Secretion

Negative Immunoregulatory Effects of Antidepressants Inhibition of Interferon-γ and Stimulation of Interleukin-10 Secretion

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

Immune Disturbances in Treatment-Resistant Depression: Modulation by Antidepressive Treatments

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