Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder

Abstract

Background: Posttraumatic stress disorder (PTSD) is associated with disturbed sleep and elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Studies in animals and healthy humans have also shown that disrupted sleep elevates pro-inflammatory cytokines, including IL-6 and TNF-α. A better understanding of overnight cytokine levels and sleep might shed light on possible mechanisms for elevated inflammation in PTSD. Thus, we investigated overnight levels of IL-6 and TNF-α in individuals with and without PTSD while recording sleep polysomnography (PSG). Method: Serum samples were collected from otherwise healthy, medication-free participants with chronic PTSD (n=44; 50% female; M age=30.34± 8.11) and matched controls (n=49; 53% female; M age=30.53± 6.57) during laboratory PSG. Levels of IL-6 and TNF-α were measured at hours 0, 2, 4, 6, and 8 after typical sleep onset time using serial serum samples. Plasma IL-6 and TNF-α levels were quantified using enzyme-linked immunosorbent assays. Results: Growth model analysis indicated a significant group by time interaction for IL-6 (t[247] = −2.92, p = .005) and a significant group by sex by time interaction for TNF-α (t[275] = 2.02, p = .04). PTSD positive men and women initially had higher IL-6 and TNF-α at sleep onset, but not at the end of their sleep cycle. Men with PTSD showed a peak of TNF-α at the end of the sleep *

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation

“…It is unclear if gonadal steroid hormones directly modulate the immunological response in PTSD, or achieve that effect via the HPA axis. While several studies have included female participants in their samples [79], only one recent study probed for sex differences in levels of pro-inflammatory cytokines in a sample of PTSD adults in comparison to age-and sexmatched controls [97]. The study demonstrated altered overnight levels of IL-6 and TNF-α in men and women with PTSD in comparison to healthy controls, but did not find any sex difference [97].…”

“…While several studies have included female participants in their samples [79], only one recent study probed for sex differences in levels of pro-inflammatory cytokines in a sample of PTSD adults in comparison to age-and sexmatched controls [97]. The study demonstrated altered overnight levels of IL-6 and TNF-α in men and women with PTSD in comparison to healthy controls, but did not find any sex difference [97]. The paucity of studies highlights the need for additional sex-based research on the role of inflammation in the pathophysiology of PTSD.…”

Posttraumatic stress disorder (PTSD), sleep, and cardiovascular disease risk: A mechanism-focused narrative review.

“…Experimental studies have shown that acute induction of partial sleep deprivation results in subsequent elevation of inflammatory cytokines implicated in atherogenesis (Meier-Ewert et al, 2004; van Leeuwen et al, 2009). Meta-analytic evidence indicates that PTSD is associated with elevated levels of several inflammatory markers (Passos et al, 2015), and there is also some evidence that overnight trajectories of proinflammatory cytokines differ in individuals with and without PTSD (Küffer et al, 2019). Additionally, sleep improvements over 3 months in previously deployed military personnel were associated with reductions in C-reactive protein over the three-month period (Heinzelmann et al, 2014), suggesting that remedying sleep disturbance after trauma might decrease inflammation.…”

Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective

“…Specifically, studies have shown that IL-6 is crucial in the relationship between immune system and CNS in inflammatory states [44]. Furthermore, 4 studies have demonstrated that individuals with PTSD have elevated proinflammatory cytokine levels when compared with healthy individuals who have not been exposed to any trauma [51][52][53][54]. In addition, studies have also demonstrated elevated CRP levels which are known to be influenced by proinflammatory cytokines, where individuals with PTSD showed increased CRP levels compared to healthy controls [42], and PTSD symptom severity were positively associated with CRP levels [50,55].…”