Role of interleukin-6 in stress, sleep, and fatigue

Ann N Y Acad Sci. 2012 Jul:1261:88-96. doi: 10.1111/j.1749-6632.2012.06634.x.


Chronic low-grade inflammation, in particular increased concentrations of proinflammatory cytokines such as interleukin (IL)-6 in the circulation, is observed with increasing age, but it is also as a consequence of various medical and psychological conditions, as well as life-style choices. Since molecules such as IL-6 have pleiotropic effects, consequences are wide ranging. This short review summarizes the evidence showing how IL-6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep-related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL-6 in the circulation. Research showing that acute as well as chronic psychological stress also increase concentrations of IL-6 supports the notion of a close link between an organism's response to physiological and psychological perturbations. The findings summarized here further underscore the particular importance of IL-6 as a messenger molecule that connects peripheral regulatory processes with the CNS.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / therapy
  • Fatigue / immunology
  • Fatigue / metabolism*
  • Humans
  • Immune System / physiology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Mice
  • Neuroimmunomodulation / immunology*
  • Sleep Wake Disorders / immunology
  • Sleep Wake Disorders / metabolism*
  • Stress, Physiological / immunology
  • Stress, Psychological / immunology
  • Stress, Psychological / metabolism*


  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • tocilizumab