Immune-to-Brain Communication Pathways in Inflammation-Associated Sickness and Depression

Curr Top Behav Neurosci. 2017:31:73-94. doi: 10.1007/7854_2016_37.


A growing body of evidence now highlights a key role for inflammation in mediating sickness behaviors and depression. Systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and chronic liver disease have high comorbidity with depression. How the periphery communicates with the brain to mediate changes in neurotransmission and thereby behavior is not completely understood. Traditional routes of communication between the periphery and the brain involve neural and humoral pathways with TNFα, IL-1β, and IL-6 being the three main cytokines that have primarily been implicated in mediating signaling via these pathways. However, in recent years communication via peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have received increasing attention for their ability to modulate brain function. In this chapter we discuss periphery-to-brain communication pathways and their potential role in mediating inflammation-associated sickness behaviors and depression.

Keywords: Cytokines; Depression; Gut microbiome; Microglia; Sickness behavior.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / metabolism*
  • Cytokines / metabolism*
  • Depressive Disorder / immunology
  • Depressive Disorder / metabolism*
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Illness Behavior / physiology*
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Signal Transduction / physiology*


  • Cytokines