Molecular mechanisms of actions of interleukin-6 on the brain, with special reference to serotonin and the hypothalamo-pituitary-adrenocortical axis

Neurochem Res. 1999 Sep;24(9):1169-80. doi: 10.1023/a:1020720722209.


Biological activities of the multifunctional cytokine, interleukin-6 (IL-6) include stimulation of B cell proliferation, immunoglobulin production, and initiation of the acute-phase response. IL-6 affects the CNS in that it activates the hypothalamo-pituitary-adrenocortical (HPA) axis and increases brain tryptophan and serotonin metabolism. IL-6 has been proposed as an important mediator of interaction between the neuroendocrine and immune systems. The peripheral and central effects of IL-6 are presumably mediated through its membrane receptor (IL-6R). IL-6, IL-6R and their respective mRNAs have been detected in several brain regions. Although the functions of cytokines overlap considerably, each displays its own characteristic properties. Expression of IL-6 in the brain has been observed in several CNS disorders, some of which have been associated with disorders of serotonin metabolism. It is proposed that interactions between IL-6 and brain serotonin is a complex process which involves corticotropin-releasing factor (CRF) and opioid peptides. It is likely that the molecular mechanisms underlying the actions of IL-6 on the HPA axis and its other brain functions involve the integrated effects of glutamate, Ca2+, 3',5'-cyclic AMP, protein kinase C, and other metabolic pathways.

Publication types

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

MeSH terms

  • Adrenal Cortex / drug effects*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Interleukin-6 / pharmacology*
  • Serotonin / metabolism*


  • Interleukin-6
  • Serotonin