Immunobiology of IL-37: mechanism of action and clinical perspectives

Abstract

This article provides an overview of the biological function of a recently discovered cytokine, IL-37, formerly referred to as IL-1F7, and its role in chronic inflammation and autoimmune disease. Much has been discovered about IL-37 in the past decade, including its ability to down-regulate systemic and local inflammation by lowering levels of pro-inflammatory molecules. Here, we critically review the published reports. Future research is necessary to understand the receptor-dependent effects of IL-37, its intracellular and extracellular functions in both normal and diseased states and its potential role as a biomarker and pharmacological target in human disease.

Keywords::

• adaptive immunity
• autoimmune disease
• IL-37
• inflammation
• innate immunity

Disclaimer

The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Financial & competing interest disclosure

This study was supported by research grants from the National Institutes of Health, USA to DK Agrawal. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• IL-37 is an anti-inflammatory cytokine that inhibits both innate and adaptive immunity by down-regulating pro-inflammatory molecules and pathways.

• Alternative splicing of IL-37 gives rise to five different isoforms: a, b, c, d and e.

• IL-37b, the most functional isoform, finds expression in cells throughout the body.

• IL-37 is upregulated as a natural defense mechanism in inflammatory states and in various autoimmune diseases.

• IL-37 expression in transgenic mice decreases the severity of IBD, severe acute hepatitis and hepatic ischemia and reperfusion.

• Increased levels of IL-37 in various cells and tissues of humans have been found in several pathological conditions or procedures, including weight reduction after gastric banding surgery, RA, IBD, hepatitis B and C, SLE, GBS, psoriasis, atherosclerosis and ACS.

• Future research should focus on the precise mechanism of action of IL-37, as well as potential therapeutic roles of IL-37 enhancement or suppression.

Notes