Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions

Ann N Y Acad Sci. 2001 Mar;933:201-10. doi: 10.1111/j.1749-6632.2001.tb05825.x.


In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Clozapine / pharmacology
  • Cytokines / pharmacology
  • Cytokines / physiology
  • Endotoxins / pharmacology
  • Fatigue / physiopathology
  • Fatigue Syndrome, Chronic / immunology
  • Fatigue Syndrome, Chronic / physiopathology*
  • Fibromyalgia / immunology
  • Fibromyalgia / physiopathology
  • Humans
  • Inflammation Mediators / pharmacology
  • Inflammation Mediators / physiology*
  • Multiple Chemical Sensitivity / immunology
  • Multiple Chemical Sensitivity / physiopathology
  • Neuroimmunomodulation / physiology
  • Receptors, Cytokine / drug effects
  • Receptors, Cytokine / physiology
  • Sleep / physiology*
  • Sleep Stages / physiology
  • Sleep Wake Disorders / physiopathology*


  • Antipsychotic Agents
  • Cytokines
  • Endotoxins
  • Inflammation Mediators
  • Receptors, Cytokine
  • Clozapine