Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells

Salas, Margarita; Evans, Stuart; Levell, M. J.; Whicher, J T

doi:10.1111/j.1365-2249.1990.tb08114.x

Cited by 168 publications

(50 citation statements)

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“…It has been shown that IL6 alone stimulates glucocorticoid release from primary cultures of rat, bovine and human adrenal cells (19)(20)(21)(22)(23). However, in order to stimulate glucocorticoid release, a long incubation time (O12 h) is required.…”

Section: Discussionmentioning

confidence: 99%

“…However, in order to stimulate glucocorticoid release, a long incubation time (O12 h) is required. IL6 also acts in synergy with ACTH, and in the presence of ACTH IL6 increases glucocorticoid release even at times when, alone, it is ineffective (19,22). In mice ACTH is a necessary permissive factor that enables IL6 to stimulate glucocorticoid secretion, at least during the first 36 h of viral infection (7).…”

Section: Discussionmentioning

confidence: 99%

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Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Žarković

Ignjatović

Dajak³

et al. 2008

European Journal of Endocrinology

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Objective: Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitaryadrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Design and methods: Basal IL6 concentration was measured and a low dose (1 mg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. Results: Data are presented as meanGS.E.M. Basal IL6 level was 0.84G0.10 pg/ml. Basal cortisol was 351.9G18.3 nmol/l. Maximal cortisol during synacthen test was 653.0G20.6 nmol/l. Maximal cortisol increment was 301.1G20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (rZ0.63, 95% confidence interval) 0.42-0.83). Conclusions: In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions. European Journal of Endocrinology 159 649-652

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Žarković

Ignjatović

Dajak³

et al. 2008

European Journal of Endocrinology

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“…This reduced GR response was related to high serum TNF-a and IL-6 levels. Since psychological or physical stress was shown to result in an enhanced IL-6 secretion in the peripheral immune system, [149][150][151] the functional relationship between cytokines and HPA axis activity is of pivotal interest in MD research. Psychological stress not only directly induce the activity of the HPA axis, but may also induce it indirectly through increased IL-6 levels.…”

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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“…Activation of the HPA axis is one of the best-documented changes in major depression (Roy et al 1987). Furthermore, the relationship between psychological or physical stress and an enhanced IL-6 secretion in the peripheral immune system seems to be well established (LeMay et al 1990;Salas et al 1990;Zhou et al 1993;Miyahara et al 2000). An impaired ability to cope with stress is often observed in depressed patients.…”

Section: Interleukin-6mentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

Mößner

Mikova

Koutsilieri

et al. 2007

The World Journal of Biological Psychiatry

226

126

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Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.

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Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells

Cited by 168 publications

References 22 publications

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

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

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

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