THE EFFECTS OF PSYCHOLOGICAL STRESS ON HUMANS: INCREASED PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND Th1-LIKE RESPONSE IN STRESS-INDUCED ANXIETY

Maes, Michaël; Song, Cai; Lin, Aihua; Jongh, R. De; Gastel, Ann Van; Kenis, Günter; Bosmans, Eugène; Meester, Ingrid De; Benoy, Ina; Neels, Hugo; Demedts, Paul; Janča, Aleksandar; Scharpé, Simon; Smith, R.S.

doi:10.1006/cyto.1997.0290

Cited by 659 publications

(443 citation statements)

References 0 publications

Supporting

Mentioning

400

Contrasting

Unclassified

Order By: Relevance

“…Transgenic mice expressing high levels of brain TNF-alpha, 48,49 as well as mice with increased hippocampal uptake of TNF-alpha following traumatic brain injury, 51 have also been shown to exhibit alterations in exploratory activity including a reduced number of rearings. Moreover, high levels of TNFalpha have been associated with symptoms of anxiety in humans under conditions of psychological stress 52 or following administration of LPS. 53 Interestingly, benzodiazepines have been shown to inhibit LPSinduced production of TNF-alpha from human microglial cells 54 and monocytes 55 as well as murine macrophages.…”

Section: Discussionmentioning

confidence: 99%

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman

MacDougall

et al. 2006

Mol Psychiatry

View full text Add to dashboard Cite

Endogenous glucocorticoids restrain proinflammatory cytokine responses to immune challenges such as viral infection. In addition, proinflammatory cytokines induce behavioral alterations including changes in locomotor/exploratory activity. Accordingly, we examined proinflammatory cytokines and open-field behavior in virally infected mice rendered glucocorticoid deficient by adrenalectomy (ADX). Mice were infected with murine cytomegalovirus (MCMV), and open-field behavior (36 h post-infection) and plasma concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 (42 h post-infection) were assessed. Compared to sham-ADX-MCMV-infected animals, ADX-MCMV-infected mice exhibited significant reductions in total distance moved, number of center entries, and time spent in center. These behavioral alterations were accompanied by significantly higher plasma concentrations of TNF-alpha and IL-6, both of which were correlated with degree of behavioral change. To examine the role of TNF-alpha in these behavioral alterations, open-field behavior was compared in wild-type (WT) and TNF-R1-knockout (KO), ADX-MCMV-infected mice. TNF-R1-KO mice exhibited significantly attenuated decreases in number of rearings, number of center entries and time spent in center, but not distance moved, which correlated with plasma IL-6. Given the potential role of brain cytokines in these findings, mRNA expression of TNF-alpha, IL-1 and IL-6 was assessed in various brain regions. Although MCMV induced increases in proinflammatory cytokine mRNA throughout the brain (especially in ADX animals), no remarkable differences were found between WT and TNF-R1-KO mice. These results demonstrate that endogenous glucocorticoids restrain proinflammatory cytokine responses to viral infection and their impact on locomotor/exploratory activity. Moreover, TNF-alpha appears to mediate cytokine-induced changes in open-field behaviors, especially those believed to reflect anxiety.

show abstract

Section: Discussionmentioning

confidence: 99%

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman

MacDougall

et al. 2006

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…In addition, psychological stress in humans significantly increases the stimulated production of pro-inflammatory cytokines, including IFN␥ (Maes et al 1998a). Humans with increased IFN␥ and decreased IL-10 secretion and, consequently, all increased IFN␥/IL-10 ratio, show significant stress-induced increments in depression and anxiety (Maes et al 1998b).…”

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

View full text Add to dashboard Cite

show abstract

“…Diluted whole blood stimulated with PHA ϩ LPS offers the most appropriate and reproducible culture condition in order to measure cytokine production De Groote et al 1992. Diluted whole blood cultures reflect the in-vivo immune cellular and humoral interactions and may be employed to examine the effects of drugs on cytokine secretion De Groote et al 1992Maes et al 1998). A total of 1.8 ml of RPMI-1640 medium with L-glutamine (Gibco BRL) supplemented with 100 IU/mL penicillin (Sigma), 100 g/mL streptomycin (Sigma), and PHA ϩ LPS were placed into 24 well cell culture plates (Falcone 3047; Becton Dickonsen).…”

Section: Methodsmentioning

confidence: 99%

“…Differences among treatment means were ascertained by means of the Dunn test. In order to examine the ratio of the secretion of pro-inflammatory (IFN ␥ ) versus negative immunoregulatory (IL-10) cytokines, the IFN ␥ /IL-10 ratio was computed as: z transformed IFN ␥ and z transformed IL-10 ( Maes et al 1998). IFN ␥ and IL-10 and their ratio were processed in Box-Cox transformation.…”

Section: Statisticsmentioning

confidence: 99%

Effects of Serotonin and Serotonergic Agonists and Antagonists on the Production of Interferon-γ and Interleukin-10

Kubera¹,

Kenis²,

Bosmans³

et al. 2000

Neuropsychopharmacology

View full text Add to dashboard Cite

(5-HT) is a neurotransmitter and an immune modulator. In vitro , antidepressants with a serotonergic mode of action have, at concentrations within the therapeutical range, negative immunoregulatory effects, i.e., they increase the production rate of interleukin-10 (IL-10), a negative immunoregulatory cytokine. We have hypothesized that part of these effects may be explained by the serotonergic activities of antidepressants on immunocytes. This study was carried out to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan , and ritanserin (a 5-HT2A/ 2C antagonist) on the production rate of interferon-␥ (IFN ␥ ), a proinflammatory cytokine, and IL-10 by whole blood stimulated with polyclonal activators. The IFN ␥ /IL-10 production ratio was computed, since this ratio reflects the pro-versus anti-inflammatory capacity of cultured whole blood. We found that: 1) 5-HT, 150 ng/mL, 1.5 g/ mL, and 15 g/mL significantly decreased the IFN ␥ /IL-10 ratio; 2) PCPA (5 M) significantly suppressed the production of 3) Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter, a vasoactive amine released by platelets at sites of inflammation and an immune modulator (Roszman et al. 1985;Mossner and Lesch 1998;Kubera and Maes 1999). In humans, 5-HT is produced, outside the central nervous system, by enterochromaffin cells and it is stored in circulating platelets and to a lesser extent in monocytes and lymphocytes (Essmann 1978). 5-HT is released from platelets and lymphocytes/monocytes following stimulation by platelet activating factors or lectins/interferon-␥ (IFN ␥ ), respectively (Finocchiaro et al. 1988 (Cohen et al. 1985;Felten et al. 1991). Pharmacological and molecular analyses have confirmed the presence of 5HT1A and 5HT2A/C receptors on activated human immunocytes and specific 5-HT transporter sites on macrophages/ lymphocytes (Aune et al. 1994).The effect of 5-HT on cell-mediated immunity and on the inflammatory response system (IRS) is still a matter of controversy. Some studies show that 5-HT has immunosuppressive effects. Devoino et al. (1968) reported that substances, which have the property to increase 5-HT concentrations, inhibit immunogenesis and antibody production in rodents. 5-HT may suppress delayed hypersensitivity and transplantation immunity (for review see Devoino and Morozova 1988). Bonnet et al. (1984) found that 5-HT suppresses murine lymphocytic response to phytohemagglutinin A (PHA) and/or allogeneic cells. p-Chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, enhances the production of antibodies . Other immune functions, however, may be stimulated by 5-HT. For example, cutaneous injection of 5-HT can initiate a delayed-type hypersensitivity reaction through local recruitment and activation of CD4 ϩ T-helper cells (Ptak et al. 1991). Low doses (100 ng/ml) of exogenously added 5-HT stimulate T cell proliferation in response to interleukin-2 (IL-2) (Young et al. 1993; Young and Mathews 1995). Enhancement of murine T-cell blastogenesis by 5-HT has b...

show abstract

THE EFFECTS OF PSYCHOLOGICAL STRESS ON HUMANS: INCREASED PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND Th1-LIKE RESPONSE IN STRESS-INDUCED ANXIETY

Cited by 659 publications

References 0 publications

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

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

Effects of Serotonin and Serotonergic Agonists and Antagonists on the Production of Interferon-γ and Interleukin-10

Contact Info

Product

Resources

About