Defective NK cell activity and Th1 response in IL-18-deficient mice

Immunity. 1998 Mar;8(3):383-90. doi: 10.1016/s1074-7613(00)80543-9.


IL-18 is a cytokine that is secreted from activated macrophages and induces IFNgamma production. To investigate the in vivo role of IL-18, we generated IL-18-deficient mice. In Propionibacterium acnes (P. acnes)-primed IL-18-deficient mice, LPS-induced IFNgamma production was markedly reduced, despite normal IL-12 induction. Natural killer cell activity was significantly impaired. Th1 cell response after injection of P. acnes or Mycobacterium bovis (bacillus Calmette-Guerin [BCG]) was significantly reduced. Similar results were observed in IL-12-deficient mice. Interestingly, Th1 response was induced after BCG infection in IL-12-deficient mice. We therefore generated mice lacking both IL-18 and IL-12. In these mice, NK activity and Th1 response were further impaired. This demonstrates the important role of both IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / blood
  • Cytokines / deficiency*
  • Cytokines / genetics
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Interleukin-18
  • Killer Cells, Natural / immunology*
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Mutant Strains
  • Mycobacterium bovis / immunology
  • Propionibacterium acnes / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology


  • Cytokines
  • Interleukin-18
  • Lipopolysaccharides
  • Interleukin-12
  • Interferon-gamma