title: Targeting IL-1 in depression.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Maes Clinics @ TRIA, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Cai
authors.initials: C
authors.lastname: Song
authors.forename: Raz
authors.initials: R
authors.lastname: Yirmiya
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1