IL-37 is a fundamental inhibitor of innate immunity

Nat Immunol. 2010 Nov;11(11):1014-22. doi: 10.1038/ni.1944. Epub 2010 Oct 10.


The function of interleukin 37 (IL-37; formerly IL-1 family member 7) has remained elusive. Expression of IL-37 in macrophages or epithelial cells almost completely suppressed production of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. Anti-inflammatory cytokines were unaffected. Mice with transgenic expression of IL-37 were protected from lipopolysaccharide-induced shock, and showed markedly improved lung and kidney function and reduced liver damage after treatment with lipopolysaccharide. Transgenic mice had lower concentrations of circulating and tissue cytokines (72-95% less) than wild-type mice and showed less dendritic cell activation. IL-37 interacted intracellularly with Smad3 and IL-37-expressing cells and transgenic mice showed less cytokine suppression when endogenous Smad3 was depleted. IL-37 thus emerges as a natural suppressor of innate inflammatory and immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Knockdown Techniques
  • Humans
  • Immunity, Innate / immunology*
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology*
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • Smad3 Protein / immunology


  • IL37 protein, human
  • Interleukin-1
  • Smad3 Protein