1. Relations of combat stress and posttraumatic stress disorder to 24-h plasma and cerebrospinal fluid interleukin-6 levels and circadian rhythmicity
- Author
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Dewleen G. Baker, Uzair Haji, Imanuel Lerman, Clara Snijders, Agorastos Agorastos, Thomas D. Geracioti, George P. Chrousos, Tobias Moeller-Bertram, Piyush M. Patel, Donald A. Barkauskas, Richard L. Hauger, Promovendi MHN, and RS: MHeNs - R3 - Neuroscience
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,medicine.disease_cause ,Systemic inflammation ,Stress Disorders, Post-Traumatic ,Plasma ,0302 clinical medicine ,Endocrinology ,Cerebrospinal fluid ,Circadian system ,Chronic stress ,Blood-brain-barrier ,DNA METHYLATION ,Veterans ,GENE-EXPRESSION ,Combat Disorders ,Cerebrospinal fluid (CSF) ,biology ,Posttraumatic stress disorder (PTSD) ,C-REACTIVE PROTEIN ,Circadian Rhythm ,Psychiatry and Mental health ,medicine.anatomical_structure ,Military Personnel ,Cytokines ,medicine.symptom ,Adult ,medicine.medical_specialty ,PTSD RISK ,Neuroimmunomodulation ,IMMUNE ,Blood–brain barrier ,Stress ,Trauma ,03 medical and health sciences ,Young Adult ,Combat stress reaction ,Internal medicine ,medicine ,Humans ,Circadian rhythm ,Interleukin 6 ,PRO-INFLAMMATORY CYTOKINES ,Biological Psychiatry ,Endocrine and Autonomic Systems ,business.industry ,Interleukin-6 ,CENTRAL-NERVOUS-SYSTEM ,MAJOR DEPRESSION ,Immune dysregulation ,030227 psychiatry ,DEPLOYED MARINES ,Immune system ,Case-Control Studies ,Interleukin-6 (IL-6) ,Serial sampling ,biology.protein ,PITUITARY-ADRENAL AXIS ,business ,030217 neurology & neurosurgery - 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.
- Published
- 2019