Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans: Relevance for symptoms of anxiety and depression

Neurosci Biobehav Rev. 2020 Aug:115:15-24. doi: 10.1016/j.neubiorev.2020.05.001. Epub 2020 May 17.


Increasing evidence from animal and human studies suggests that inflammation may be involved in mood disorders. Sickness behavior and emotional changes induced by experimental inflammatory stimuli have been extensively studied in humans and rodents to better understand the mechanisms underlying inflammation-driven mood alterations. However, research in animals and humans have remained compartmentalized and a comprehensive comparison of inflammation-induced sickness and depressive-like behavior between rodents and humans is lacking. Thus, here, we highlight similarities and differences in the effects of bacterial lipopolysaccharide administration on the physiological (fever and cytokines), behavioral and emotional components of the sickness response in rodents and humans, and discuss the translational challenges involved. We also emphasize the differences between observable sickness behavior and subjective sickness reports, and advocate for the need to obtain both subjective reports and objective measurements of sickness behavior in humans. We aim to provide complementary insights for translational clinical and experimental research on inflammation-induced behavioral and emotional changes, and their relevance for mood disorders such as depression.

Keywords: Depressive-like behavior; Fever; Humans; Inflammation; Lipopolysaccharide; Rodents; Sickness behavior; Translational research.

Publication types

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

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Behavior, Animal
  • Cytokines
  • Depression / chemically induced
  • Humans
  • Illness Behavior*
  • Inflammation / chemically induced
  • Lipopolysaccharides*
  • Rodentia


  • Cytokines
  • Lipopolysaccharides