Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1β

J Immunol. 2017 Jun 1;198(11):4210-4215. doi: 10.4049/jimmunol.1700352. Epub 2017 May 3.


Interleukin-18 and IL-1β, which are cytokines of the IL-1 family, are synthesized as precursor proteins and activated by the inflammasome via proteolytic processing. IL-1β is only induced in response to inflammatory stimuli, but IL-18 is constitutively expressed. However, how IL-18 and IL-1β expression is regulated by different inflammatory signals remains poorly studied. In this study, we found that IL-18 and IL-1β are differentially regulated. Despite being constitutively expressed, IL-18 expression was increased and sustained after stimulation of TLRs. In contrast, IL-1β was induced but not sustained after chronic treatment. Furthermore, type I IFN signaling was essential for induction of IL-18 and macrophages lacking type I IFN signaling were impaired in their ability to promote IL-18 induction. Thus, our findings reveal a fundamental difference in IL-18 and IL-1β regulation and uncover novel mechanisms that are relevant to the inflammatory settings where these proinflammatory cytokines play a critical role.

Publication types

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

MeSH terms

  • Aminoquinolines / pharmacology
  • Animals
  • Cells, Cultured
  • Gene Expression Regulation*
  • Imidazoles / pharmacology
  • Inflammasomes / immunology
  • Interferon Type I / deficiency
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interleukin-18 / genetics*
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Signal Transduction* / genetics
  • Toll-Like Receptors / immunology


  • Aminoquinolines
  • Imidazoles
  • Inflammasomes
  • Interferon Type I
  • Interleukin-18
  • Interleukin-1beta
  • Toll-Like Receptors
  • gardiquimod