Longitudinal Changes in Sleep: Associations with Shifts in Circulating Cytokines and Emotional Distress in a Cancer Survivor Population

Abstract

Background Sleep disturbances are associated with numerous mood disorders. Similarly, anxiety and depression are associated with modulation of the psychoneuroimmune (PNI) axis. This study hypothesized that changes in both monitored and self-reported measures of sleep would relate to changes in circulating cytokine levels in an emotionally distressed population of cervical cancer survivors. Methods Biospecimens, patient-reported outcome (PRO) measures, and actigraphy were collected from cervical cancer survivors enrolled in a biobehavioral clinical trial. Longitudinal changes over a 4-month period were examined. Sleep time measured by actigraphy and PRO were analyzed for correlative changes with emotional distress and serum cytokines (n = 71). Results Longitudinal change in the actigraph measure of sleep time was inversely associated with changes in depression and anxiety (test for linear trend, p = 0.02 and p = 0.05 respectively), as well as acute-phase response/pro-inflammatory cytokines (test for linear trend, p = 0.003, interleukin (IL)-2; 0.022, IL-1β; 0.0002, IL-6; and 0.049, tumor necrosis factor α). Conversely, changes in self-reported sleep problems were related to an increase in depression and anxiety (p = 0.001 and p = 0.01 respectively), the T helper 2 (Th2) cytokine IL-5 (p = 0.027), and the counter-regulatory cytokine IL-10 (0.016). Conclusion This study showed that an increase in sleep time or decrease in sleep problems corresponded with a reduction in self-reported emotional distress and attenuation of pro-inflammatory, Th2, and counter-regulatory cytokines. Our results support sleep measurement as a meaningful biobehavioral variable in cancer survivorship. This study also indicates that sleep investigators should be aware that choice of methodology might influence concordance with different classes of immune parameters.

Opposing inflammatory biomarker responses to sleep disruption in cancer patients before and during oncological therapy

“…Indeed, plasma concentrations of pro-inflammatory biomarkers were found to increase several fold during oncological therapy but only in patients whose sleep quality concurrently deteriorated during this period. These findings are in line with previous studies showing that pro-inflammatory biomarkers such as IL-1b, IL-2, IL-6, IL-12, and TNF-a increase in cancer patients following a period of sleep disruption ( Mantovani et al, 2008 ; Jensen et al, 2021 ; Tucker et al, 2021 ). Surprisingly, patients reporting improved sleep quality during oncological therapy exhibited reduced plasma levels of pro-inflammatory cytokines clearly demonstrating that sleep disruption rather than cytostatic or cytotoxic therapy is driving the increased systemic inflammation observed in these patients.…”

“…In such studies, survivors of childhood ALL exhibiting poor sleep were found to have elevated plasma levels of IL-6, IL1b and CRP ( Cheung et al, 2017 ), and elevated IL-6 levels were correlated to poor sleep in non-small cell lung cancer patients receiving chemoradiotherapy ( Wang et al, 2010 ). Tucker et al found that IL-2, IL-1b, and IL-6 were upregulated in cancer survivors exhibiting reduced sleep duration based on actigraph measurements, but not in patients with self-reported sleep disruption where instead IL-10 were found to be upregulated ( Tucker et al, 2021 ). Here we took a different approach by keeping the inclusion criteria broad: All cancer patients with performance status 0 or 1, scheduled for oncological therapy were invited to participate regardless of age, gender, cancer type, tumor stage, type of planned oncological therapy, pre-treatment status, prior surgery, etc.…”

Body image and the level of stress in cervical cancer patients

“…The data collection tool uses a questionnaire body image and Depression Anxiety Stress Scale (DASS). The result of Body image is categorized as good (mean ≥) and poor (mean <23) while DASS is categorized as normal (0-14), mild (15)(16)(17)(18), moderate (19)(20)(21)(22)(23)(24)(25), severe (26)(27)(28)(29)(30)(31)(32)(33) and extreme severe (≥ 34). Body image questionnaire is valid (0,353-0,754) and reliable (Cronbach's alpha 0.483).…”

“…27 It will cause the increasing sleep time or decrease in sleep problems corresponded with a reduction in self-reported emotional distress and attenuation of pro-inflammatory, Th2, and counter-regulatory cytokines. 28 The body images are correlated to the stress level of cervical cancer patients who received chemotherapy in the Gynecology Centers of Dr. Kariadi General Hospital Medical Center. Patients' average body image was categorized as good but those with the lowest score thought that the disease, along with the chemotherapy, resulted in worse body condition, hair loss, weakness, fatigue, loss of appetite, and less social contact as the loss of confidence regarding the physical changes.…”

A Review of the Role of Interleukin-2 in the Pathophysiology of Major Depressive Disorder in Hospitalized Patients

“…83 Major depression leads to severe disorders in the personal, social and employment life of the affected person and affects the person's health. 84 Depression has different types with different intensities, and therefore complications such as inflammation will be different in these patients. In this study, we review major depression and the inflammatory factor IL-2.…”