Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events

Maes, Michaël; Lin, Aihua; Delmeire, Laure; Gastel, Ann Van; Kenis, Günter; Jongh, R. De; Bosmans, Eugène

doi:10.1016/s0006-3223(98)00131-0

Cited by 324 publications

(212 citation statements)

References 51 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…Indeed, both of these disorders have been found to be associated with an exaggerated inflammatory responses including increases in plasma concentrations of TNF-alpha and IL-6, and both are associated with increased symptoms of anxiety and alterations in locomotor activity, including psychomotor slowing and fatigue. [61][62][63][64] It has also been suggested that proinflammatory cytokines may contribute to some of the behavioral features of other disorders including chronic fatigue syndrome and fibromyalgia, which are also characterized by reduced glucocorticoids and increased proinflammatory cytokines. 61,65,66 Several limitations of this study warrant further consideration.…”

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

“…The current literature provides accruing evidence for excessive peripheral inflammation in PTSD. Evaluation of basal or stimulated peripheral cytokines (Maes et al, 1999;Spivak et al, 1997;Wong et al, 2000;Bob et al, 2010;Gill et al, 2010;Hoge et al, 2009;Symes et al, 2010;Tucker et al, 2010;von Känel et al, 2010;Lindqvist et al, 2014;Tursich et al, 2014;Plantinga et al, 2013) indicates there are abnormally increased concentrations of proinflammatory cytokines in patients with PTSD in most, but not all studies (de Kloet et al, 2007;Miller et al, 2001;Song et al, 1999). Few studies have examined cytokine levels in the CSF of individuals with PTSD.…”

Section: Inflammation and Ptsdmentioning

confidence: 99%

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Lerman

Davis

Bertram

et al. 2016

Psychoneuroendocrinology

View full text Add to dashboard Cite

a b s t r a c tObjective: Although posttraumatic stress disorder (PTSD) and chronic pain frequently occur in tandem, the pathophysiological mechanisms mediating this comorbidity are poorly understood. Because excessive inflammation occurs in both conditions, we examined the cerebrospinal fluid (CSF) concentrations of inflammatory response mediators interleukin 1-beta (IL-1␤), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF␣) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC). Methods: After completing baseline quantitative sensory testing (QST) and psychological profiling, all patients received an injection of capsaicin into the quadriceps muscle. Spontaneously reported pain was measured for 30 min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110 min post capsaicin injection. Inflammatory (IL-1␤, IL-6, IL-8 TNF␣) and antiinflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110 min. Results: Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNF␣, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1␤ significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10 min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70 min post injection. Conclusion: These findings show significant central nervous system (CNS) differences in the inflammatory response to a deep pain stimulus in combat veterans with and without PTSD. They support the concept that abnormally elevated neuroinflammatory response to pain stimuli may be one CNS mechanism accounting for the high co-occurrence of PTSD and pain.Published by Elsevier Ltd.

show abstract

“…[12,13]). Elevated levels of pro-inflammatory cytokines IL-1b, TNF-a and IL-6 has been reported in patients suffering from neuropsychiatric disorders [12,[14][15][16]. In addition, immune activation in human disease as well as in animal models is often accompanied by a discrete set of psychiatric and behavioral alterations which bear many of the hallmarks of depressive illness [17,18].…”

Section: Introductionmentioning

confidence: 99%

The Pro-inflammatory Cytokine TNF-α Regulates the Activity and Expression of the Serotonin Transporter (SERT) in Astrocytes

et al. 2013

View full text Add to dashboard Cite

Pro-inflammatory cytokines have been implicated in the precipitation of depression and related disorders, and the antidepressant sensitive serotonin transporter (SERT) may be a major target for immune regulation in these disorders. Here, we focus on astrocytes, a major class of immune competent cells in the brain, to examine the effects of pro-longed treatment with tumor necrosis factoralpha (TNF-a) on SERT activity. We first established that high-affinity serotonin uptake into C6 glioma cells occurs through a SERT-dependent mechanism. Functional SERT expression is also confirmed for primary astrocytes. In both cell types, exposure to TNF-a resulted in a dose-and timedependent increase in SERT-mediated 5-HT uptake, which was sustained for at least 48 h post-stimulation. Further analysis in primary astrocytes revealed that TNF-a enhanced the transport capacity (V max ) of SERT-specific 5-HT uptake, suggesting enhanced transporter expression, consistent with our observation of an increase in SERT mRNA levels. We confirmed that in both, primary astrocytes and C6 glioma cells, treatment with TNF-a activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment with the p38 MAPK inhibitor SB203580 attenuated the TNF-a mediated stimulation of 5-HT transport in both, C6 glioma and primary astrocytes. In summary, we show that SERT gene expression and activity in astrocytes is subject to regulation by TNF-a, an effect that is at least in part dependent on p38 MAPK activation.

show abstract

Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events

Cited by 324 publications

References 51 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

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

The Pro-inflammatory Cytokine TNF-α Regulates the Activity and Expression of the Serotonin Transporter (SERT) in Astrocytes

Contact Info

Product

Resources

About