Cytokines in sleep regulation

Adv Neuroimmunol. 1995;5(2):171-88. doi: 10.1016/0960-5428(95)00007-o.


The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process results from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects neurons and glia. Evidence in support of these postulates is reviewed in this essay.

Publication types

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

MeSH terms

  • Acute-Phase Reaction
  • Amino Acid Sequence
  • Bacterial Infections / complications
  • Bacterial Infections / physiopathology
  • Cell Wall / chemistry
  • Cytokines / physiology*
  • Growth Hormone-Releasing Hormone / physiology
  • Molecular Sequence Data
  • Muramic Acids / pharmacology
  • Neuroimmunomodulation / physiology
  • Neurons / physiology
  • RNA, Double-Stranded / pharmacology
  • RNA, Viral / pharmacology
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / physiopathology
  • Virus Diseases / complications
  • Virus Diseases / physiopathology


  • Cytokines
  • Muramic Acids
  • RNA, Double-Stranded
  • RNA, Viral
  • Growth Hormone-Releasing Hormone