Interleukin-6 and the soluble IL-6 receptor are decreased in cerebrospinal fluid of geriatric patients with major depression: no alteration of soluble gp130

Stübner, Susanne; Schön, Tanja; Padberg, Frank; Teipel, Stefan J.; Schwarz, Markus J.; Haslinger, Andreas; Buch, Katharina; Dukoff, Ruth; Lasser, Robert; Müller, Norbert; Sunderland, Trey; Rapoport, Stanley I.; Möller, Hans‐Jürgen; Hampel, Harald

doi:10.1016/s0304-3940(98)00916-1

Cited by 53 publications

(32 citation statements)

References 24 publications

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“…A preliminary report of elevated plasma IL-6 and sIL-6R levels in PTSD was recently published [68]. Whereas we have been unable to locate published reports of CNS IL-6 concentrations in PTSD, cerebrospinal fluid (CSF) levels of IL-6 in depression were recently found to be decreased [69,70].…”

Section: Introductionmentioning

confidence: 84%

Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder

Baker

Ekhator

Kasckow

et al. 2001

Neuroimmunomodulation

204

113

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Background: Interleukin-6 (IL-6) secretion is suppressed by glucocorticoids and stimulated by catecholamines. Patients with posttraumatic stress disorder (PTSD) have decreased cortisol and increased catecholamine secretion. The purpose of this study was to assess the relation of IL-6 levels and hypothalamic-pituitary-adrenal and noradrenergic activity in patients with well-characterized PTSD. Methods: Cerebrospinal fluid (CSF) was withdrawn via a lumbar subarachnoid catheter over 6 h from 11 combat veterans with PTSD and 8 age- and sex-matched healthy controls. Blood was withdrawn concurrently. We measured IL-6, CRH and norepinephrine concentrations in the CSF and IL-6, ACTH, cortisol and norepinephrine in plasma. Results: Mean and median CSF IL-6 concentrations were higher in PTSD than in controls (mean = 24.0 vs. 14.6, p = 0.05; median = 26.7 vs. 14.3, p < 0.03): plasma IL-6 concentrations, however, were not different between the two groups. Plasma IL-6 and norepinephrine were positively correlated in the PTSD group (r = +0.74, p < 0.04), but not in normals (r = –0.55, p = 0.20). Conclusions: PTSD patients have increased CSF concentrations of IL-6. Their plasma IL-6 is not elevated but is more tightly associated with noradrenergic output in these patients than in normals. Both findings might be explained by the low cortisol secretion previously reported in PTSD as a result of lowered glucocorticoid suppression of IL-6 secretion. High levels of CSF IL-6 may reflect neurodegeneration or compensatory neuroprotection.

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Section: Introductionmentioning

confidence: 84%

Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder

Baker

Ekhator

Kasckow

et al. 2001

Neuroimmunomodulation

204

113

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“…92 In contrast, CSF levels of IL-6 and soluble IL-6 receptor were found to be markedly reduced in geriatric patients suffering from depression. 112 Another study investigating depressed patients of age 18-66 could not find any alteration of IL-6 levels in the CSF. 113 Levine et al 89 compared serum and CSF cytokine levels in depressed patients and healthy control persons and found significantly elevated serum levels of IL-6, but decreased IL-6 levels in CSF.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 93%

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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“…One study found that depressed patients had higher CSF concentrations of IL-1 , lower IL-6 and no change in TNF compared to normal controls [54]. Stübner et al, [55] confirmed the decreased level of IL-6 and also of soluble IL-6 receptor, this time in geriatric patients with major depression. There are also some reports of increased PGE 2 in CSF during depression [45].…”

Section: Inflammation In Csf and Cns In Depressed Individualsmentioning

confidence: 96%

Depression has a Strong Relationship to Alterations in the Immune, Endocrine and Neural System

Hestad¹,

Aukrust²,

Tønseth³

et al. 2009

CPSR

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Epidemiological findings indicate a connection between depressive symptoms and changes in status of the immune system in depressed patients. This raises the possibility of causative connections. Theories on mechanisms for interactions between immune and affective systems -directly and via endocrine system -are evolving. Such hypothesized causative connections are supported by several findings. First, in depressed patients changes in the status of the immune system in vivo and ex vivo are seen. Also, depressive symptoms are seen in patients with altered immune status (physiologically, pathologically or chemically induced). Knowledge in this field may have implications regarding psychiatric follow up of physically ill people suffering from diseases caused by an altered immune system (long lasting infections, autoimmune diseases, hypersensitivity disorders) as well as disorders for which treatment and prognoses depends on the immune system (infections, cancer). Similarly, medical treatment of depressed patients may be adjusted by more specific knowledge about the interaction between neuroimmunology and depression. Important findings and the present knowledge and theories are reviewed.

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Interleukin-6 and the soluble IL-6 receptor are decreased in cerebrospinal fluid of geriatric patients with major depression: no alteration of soluble gp130

Cited by 53 publications

References 24 publications

Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder

Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder

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

Depression has a Strong Relationship to Alterations in the Immune, Endocrine and Neural System

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