Sleep disturbance, cytokines, and fatigue in women with ovarian cancer

Brain Behav Immun. 2012 Oct;26(7):1037-44. doi: 10.1016/j.bbi.2012.04.003. Epub 2012 Apr 21.


Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been implicated in the underlying processes contributing to sleep regulation and fatigue. Despite evidence for sleep difficulties, fatigue, and elevations in IL-6 among women with ovarian cancer, the association between these symptoms and IL-6 has not been investigated. To address this knowledge gap, we examined relationships between sleep disturbance, fatigue, and plasma IL-6 in 136 women with ovarian cancer prior to surgery. These relationships were also examined in 63 of these women who were disease-free and not receiving chemotherapy one year post-diagnosis. At both time-points, higher levels of IL-6 were significantly associated with sleep disturbances (p<0.05), controlling for potentially confounding biological and psychosocial covariates. Higher IL-6 was significantly associated with fatigue prior to surgery (p<0.05); however, when sleep disturbance was included in the model, the relationship was no longer significant. IL-6 was not significantly associated with fatigue at one year. Changes in sleep over time were significantly associated with percent change in IL-6 from pre-surgery to one year, adjusting for covariates (p<0.05). These findings support a direct association of IL-6 with sleep disturbances in this population, whereas the relationship between IL-6 and fatigue prior to surgery may be mediated by poor sleep. As this study is the first to examine cytokine contributions to sleep and fatigue in ovarian cancer, further research is warranted to clarify the role of biological correlates of sleep and fatigue in this population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Affect / physiology
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Anxiety / psychology
  • Body Mass Index
  • Cytokines / blood*
  • Demography
  • Fatigue / etiology*
  • Female
  • Health Behavior
  • Humans
  • Interleukin-6 / blood
  • Middle Aged
  • Ovarian Neoplasms / complications*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / surgery
  • Sleep Wake Disorders / etiology*
  • Treatment Outcome


  • Antineoplastic Agents
  • Cytokines
  • Interleukin-6