Relations of combat stress and posttraumatic stress disorder to 24-h plasma and cerebrospinal fluid interleukin-6 levels and circadian rhythmicity

Agorastos Agorastos, Richard L. Hauger, Donald A. Barkauskas, Imanuel R. Lermana, Tobias Moeller-Bertram, Clara Snijders, Uzair Haji, Piyush M. Patel, Thomas D. Geracioti, George P. Chrousos, Dewleen G. Baker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Background: Acute and chronic stress can lead to a dysregulation of the immune response. Growing evidence suggests peripheral immune dysregulation and low-grade systemic inflammation in posttraumatic stress disorder (PTSD), with numerous reports of elevated plasma interleukin-6 (IL-6) levels. However, only a few studies have assessed IL-6 levels in the cerebrospinal fluid (CSF). Most of those have used single time-point measurements, and thus cannot take circadian level variability and CSF-plasma IL-6 correlations into account.

Methods: This study used time-matched, sequential 24-h plasma and CSF measurements to investigate the effects of combat stress and PTSD on physiologic levels and biorhythmicity of IL-6 in 35 male study volunteers, divided in 3 groups: (PTSD = 12, combat controls, CC = 12, and non-deployed healthy controls, HC = 11).

Results: Our findings show no differences in diurnal mean concentrations of plasma and CSF IL-6 across the three comparison groups. However, a significantly blunted circadian rhythm of plasma IL-6 across 24 h was observed in all combat-zone deployed participants, with or without PTSD, in comparison to HC. CSF IL-6 rhythmicity was unaffected by combat deployment or PTSD.

Conclusions: Although no significant group differences in mean IL-6 concentration in either CSF or plasma over a 24-h timeframe was observed, we provide first evidence for a disrupted peripheral IL-6 circadian rhythm as a sequel of combat deployment, with this disruption occurring in both PTSD and CC groups. The plasma IL-6 circadian blunting remains to be replicated and its cause elucidated in future research.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalPsychoneuroendocrinology
Volume100
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Interleukin-6 (IL-6)
  • Cytokines
  • Stress
  • Trauma
  • Posttraumatic stress disorder (PTSD)
  • Circadian system
  • Immune system
  • Cerebrospinal fluid (CSF)
  • Plasma
  • Neuroimmunomodulation
  • Blood-brain-barrier
  • Serial sampling
  • C-REACTIVE PROTEIN
  • PRO-INFLAMMATORY CYTOKINES
  • PITUITARY-ADRENAL AXIS
  • CENTRAL-NERVOUS-SYSTEM
  • GENE-EXPRESSION
  • MAJOR DEPRESSION
  • DEPLOYED MARINES
  • DNA METHYLATION
  • PTSD RISK
  • IMMUNE

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