Targeting IL-1 in depression

Expert Opin Ther Targets. 2012 Nov;16(11):1097-112. doi: 10.1517/14728222.2012.718331. Epub 2012 Aug 27.


Introduction: Depression is associated with inflammation, Th1 and Th17 responses, oxidative and nitrosative stress (O&NS), autoimmune responses against neoantigenic determinants, and neuroprogression (i.e., neurodegeneration, impaired plasticity and reduced neurogenesis). These pathways involve increased monocytic activation and interleukin-1 (IL-1) levels.

Areas covered: This review will highlight the putative role of IL-1 in depression and the potential use of IL-1 signaling blockade as a treatment of depression. Electronic databases, i.e., Scopus, PUBMED and Google Scholar were employed using keywords: depression, depressive-like, interleukin-1, and interleukin-1 receptor antagonist (IL-1RA).

Expert opinion: Ample studies show that depression is accompanied by increased levels of IL-1 and IL-1RA, which attenuates the pro-inflammatory activities of IL-1. In some, but not all studies, antidepressant treatment decreased IL-1β levels. In translational models, IL-1β administration elicits depressive-like behaviors, neuroinflammation and neuroprogression, whereas treatment with IL-1RA yields antidepressant-like effects and attenuates neuroprogression. Anakinra, an IL-1RA, targets not only IL-1 signaling, but also Th1, Th17, O&NS and neuroprogressive pathways and therefore may be advanced to clinical Phase-II trials in depression due to medical conditions associated with an elevated IL-1/IL-1RA ratio.

Publication types

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

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depression / metabolism*
  • Humans
  • Inflammation / metabolism
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1 / metabolism*


  • Antidepressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1