Defective NK cell activity and Th1 response in IL-18-deficient mice.
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.
Takeda
K
K
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Tsutsui
H
H
Yoshimoto
T
T
Adachi
O
O
Yoshida
N
N
Kishimoto
T
T
Okamura
H
H
Nakanishi
K
K
Akira
S
S
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood / Q000172:deficiency / Q000235:genetics; D020382:Interleukin-18; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009163:Mycobacterium bovis / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma