Release of interleukin-1 α or interleukin-1 β depends on mechanism of cell death

Hazel England, Holly Summersgill, Michelle Edye, Nancy Rothwell, David Brough

Research output: Contribution to journalArticlepeer-review


The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. We discovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1β. Conversely, necroptosis caused the processing and release of IL-1α, and this was independent of IL-1β processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
Original languageEnglish
Pages (from-to)15942-15950
Number of pages9
JournalJournal of Biological Chemistry
Issue number23
Early online date30 Apr 2014
Publication statusPublished - 6 Jun 2014


  • Apoptosis
  • Calpain
  • Caspase
  • Cell Death
  • Inflammation
  • Interleukin
  • Macrophage
  • Necrosis (Necrotic Death)

Research Beacons, Institutes and Platforms

  • Dementia@Manchester


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