Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation

Immunity. 2000 May;12(5):581-90. doi: 10.1016/s1074-7613(00)80209-5.


Caspases are intracellular proteases that mediate mammalian cell apoptosis. Caspase-1 (Casp-1) is a unique caspase because it activates the proinflammatory cytokines interleukin (IL)-1beta and IL-18. Shigella flexneri, the etiological agent of bacillary dysentery, induces macrophage apoptosis, which requires Casp-1 and results in the release of mature IL-1beta and IL-18. Here we show that casp-1(-/-) mice infected with S. flexneri do not develop the acute inflammation characteristic of shigellosis and are unable to resolve the bacterial infection. Using casp-1(-/-) mice supplemented with recombinant cytokines and experiments with IL-1beta(-/-) and IL-18(-/-) mice, we show that IL-1beta and IL-18 are both required to mediate inflammation in S. flexneri infections. Together, these data demonstrate the importance of Casp-1 in acute inflammation and show the different roles of its substrates, IL-1beta and IL-18, in this response.

Publication types

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

MeSH terms

  • Animals
  • Caspase 1 / immunology*
  • Dysentery, Bacillary / immunology*
  • Dysentery, Bacillary / metabolism
  • Immunohistochemistry
  • Inflammation / immunology
  • Interleukin-1 / immunology*
  • Interleukin-18 / immunology*
  • Mice
  • Shigella flexneri*
  • Substrate Specificity / immunology


  • Interleukin-1
  • Interleukin-18
  • Caspase 1