TY - JOUR
T1 - Relations of combat stress and posttraumatic stress disorder to 24-h plasma and cerebrospinal fluid interleukin-6 levels and circadian rhythmicity
AU - Agorastos, Agorastos
AU - Hauger, Richard L.
AU - Barkauskas, Donald A.
AU - Lermana, Imanuel R.
AU - Moeller-Bertram, Tobias
AU - Snijders, Clara
AU - Haji, Uzair
AU - Patel, Piyush M.
AU - Geracioti, Thomas D.
AU - Chrousos, George P.
AU - Baker, Dewleen G.
N1 - Funding Information:
Funding support for this work was provided by the VA Clinical Services Research and Development (CSR&D Merit Review) Program (DGB, 2004-2008) and the VA Center of Excellence for Stress and Mental Health (DGB and RLH) .
Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Interleukin-6 (IL-6)
KW - Cytokines
KW - Stress
KW - Trauma
KW - Posttraumatic stress disorder (PTSD)
KW - Circadian system
KW - Immune system
KW - Cerebrospinal fluid (CSF)
KW - Plasma
KW - Neuroimmunomodulation
KW - Blood-brain-barrier
KW - Serial sampling
KW - C-REACTIVE PROTEIN
KW - PRO-INFLAMMATORY CYTOKINES
KW - PITUITARY-ADRENAL AXIS
KW - CENTRAL-NERVOUS-SYSTEM
KW - GENE-EXPRESSION
KW - MAJOR DEPRESSION
KW - DEPLOYED MARINES
KW - DNA METHYLATION
KW - PTSD RISK
KW - IMMUNE
U2 - 10.1016/j.psyneuen.2018.09.009
DO - 10.1016/j.psyneuen.2018.09.009
M3 - Article
C2 - 30390522
SN - 0306-4530
VL - 100
SP - 237
EP - 245
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
ER -