Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme

Immunity. 2015 Jun 16;42(6):991-1004. doi: 10.1016/j.immuni.2015.06.003.


Members of the extended interleukin-1 (IL-1) cytokine family, such as IL-1, IL-18, IL-33, and IL-36, play a pivotal role in the initiation and amplification of immune responses. However, deregulated production and/or activation of these cytokines can lead to the development of multiple inflammatory disorders. IL-1 family members share a broadly similar domain organization and receptor signaling pathways. Another striking similarity between IL-1 family members is the requirement for proteolytic processing in order to unlock their full biological potential. Although much emphasis has been put on the role of caspase-1, another emerging theme is the involvement of neutrophil- and mast cell-derived proteases in IL-1 family cytokine processing. Elucidating the regulation of IL-1 family members by proteolytic processing is of great interest for understanding inflammation and immunity. Here, we review the identity of the proteases involved in the proteolytic processing of IL-1 family cytokines and the therapeutic implications in inflammatory disease.

Publication types

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

MeSH terms

  • Animals
  • Caspase 1 / metabolism*
  • Humans
  • Immunity
  • Inflammation / immunology*
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Mast Cells / immunology*
  • Neutrophils / immunology*
  • Peptide Hydrolases / metabolism
  • Proteolysis*


  • Interleukin-1
  • Peptide Hydrolases
  • Caspase 1