Mechanisms of unconventional secretion of IL-1 family cytokines

Cytokine. 2015 Aug;74(2):213-8. doi: 10.1016/j.cyto.2015.03.022. Epub 2015 Apr 25.


One of the most poorly understood processes in cell biology is the peculiar ability of specific leaderless proteins to be secreted via ER/Golgi-independent mechanisms ('unconventional protein secretion'). One such leaderless protein is the major immune-activating cytokine, interleukin-1β (IL-1β). Unusual amongst cytokines, IL-1β is expressed in the cytosol as an inactive precursor protein. It requires maturation by the caspase-1 protease, which itself requires activation upon immune cell sensing of infection or cell stress. Despite 25 years of intensive research into IL-1β secretory mechanisms, how it exits the cell is still not well understood. Here we will review the various mechanisms by which macrophages have been proposed to secrete IL-1 family cytokines, and the potential involvement of caspase-1 therein. Since aberrant IL-1β production drives inherited and acquired human diseases (e.g. autoinflammatory diseases, arthritic diseases, gout, Alzheimer's disease), elucidation of the IL-1β secretory pathway may offer new therapeutic opportunities for treatment across this wide range of human conditions.

Keywords: Caspase-1; Inflammasome; Interleukin-1; Unconventional secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / immunology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Arthritis / immunology*
  • Arthritis / metabolism
  • Arthritis / pathology
  • Caspase 1 / immunology*
  • Caspase 1 / metabolism
  • Gout / immunology*
  • Gout / metabolism
  • Gout / pathology
  • Humans
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology


  • IL1B protein, human
  • Interleukin-1beta
  • Caspase 1