Targeting IL-1 in depression

Michael Maes, Cai Song*, Raz Yirmiya

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

135 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1097-1112
Number of pages16
JournalExpert Opinion on Therapeutic Targets
Volume16
Issue number11
DOIs
StatePublished - Nov 2012

Bibliographical note

Funding Information:
All in all, although the increase in IL-1 levels is certainly not the only driver of activated immuno-inflammatory pathways in depression, Anakinra and other blockers of IL-1 signaling may attenuate the different cellular and molecular pathways that play a role in depression. Therefore, we think that Anakinra has the potential to be advanced to Phase-II clinical trials in patients with depression due to medical conditions associated with elevated IL-1b levels and IL-1/IL-1RA ratio, such as RA and diabetes. In case of positive results, subsequent studies should be conducted in patients with other forms of depression associated with activated IL-1 signaling. In these studies the IL-1 blockers may be examined both as supplementary adjuvant drugs along with conventional antidepressants or as stand-alone drugs (particularly when IL-1 blockade is warranted for treatment of a co-morbid medical condition other than depression). CS was supported by Canadian Institute for Health research (CIHR) operating grants (grant no. 89966).

Funding Information:
The authors have received financial support from the Legacy Heritage Biomedical Program of the Israel Science Foundation (grant no. 430/09).

Keywords

  • Antidepressants.
  • Cytokines
  • Depression
  • Inflammation
  • Interleukin-1

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