Cytokine-induced sickness behavior: mechanisms and implications

Ann N Y Acad Sci. 2001 Mar;933:222-34. doi: 10.1111/j.1749-6632.2001.tb05827.x.


Sickness behavior refers to a coordinated set of behavioral changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the brain effects of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha). Peripherally released cytokines act on the brain via a fast transmission pathway involving primary afferent nerves innervating the bodily site of inflammation and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission. At the behavioral level, sickness behavior appears to be the expression of a central motivational state that reorganizes the organism priorities to cope with infectious pathogens. There is evidence that the sickness motivational state can interact with other motivational states and respond to nonimmune stimuli probably by way of sensitization and/or classical conditioning. However, the mechanisms that are involved in plasticity of the sickness motivational state are not yet understood.

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Afferent Pathways / physiology
  • Amygdala / physiology
  • Animals
  • Appetitive Behavior / physiology
  • Brain / physiopathology
  • Choroid Plexus / physiology
  • Cytokines / physiology*
  • Depression / etiology
  • Depression / physiopathology
  • Exploratory Behavior
  • Fever / physiopathology
  • Humans
  • Infections / immunology
  • Infections / physiopathology
  • Infections / psychology
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Inflammation / psychology
  • Interleukin-1 / physiology
  • Learning Disabilities / etiology
  • Learning Disabilities / physiopathology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mood Disorders / etiology
  • Mood Disorders / physiopathology
  • Motivation
  • Neuroimmunomodulation / physiology
  • Rats
  • Sick Role*
  • Tumor Necrosis Factor-alpha / physiology
  • Vagus Nerve / physiology


  • Cytokines
  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha