Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection.
Various bacterial pathogens have been identified as mediators of apoptosis. Apoptosis reportedly shows both detrimental and beneficial effects on biological functions. We studied the role of liver apoptosis in lethal Listeria monocytogenes infection and the regulation of apoptosis by endogenous cytokines during infection. Apoptosis was observed in the spleen but not in the liver of infected mice, whereas the induction of liver necrosis was evident by rising levels of serum aminotransferases in these animals. Apoptosis was detected in the liver of L. monocytogenes-infected mice which had been treated with monoclonal antibody (mAb) against tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), or in TNF-alpha(-/-) mice, but not in gamma- interferon (IFN-gamma)(-/-) mice or mice which had been treated with mAb against IL-4 or IL-10. Augmentation of liver apoptosis in mice treated with mAb against TNF-alpha or IL-6 or in TNF-alpha(-/-) mice correlated with the increase in bacterial numbers in the organ, while no augmentation of apoptosis was observed in the liver of IFN-gamma(-/-) mice irrespective of the marked increase in bacterial numbers in the organs, indicating that augmentation of liver apoptosis may not be merely due to the increase in bacterial growth in the organs. These results suggest that TNF-alpha and IL-6 may play an important role in protecting the liver from apoptosis in lethal L. monocytogenes infection.
Miura
T
T
Department of Bacteriology, Hirosaki Unversity School of Medicine, Hirosaki-Aomori, Japan.
Nishikawa
S
S
Sasaki
S
S
Yamada
K
K
Hasegawa
S
S
Mizuki
D
D
Mizuki
M
M
Hatayama
I
I
Sekikawa
K
K
Tagawa
Y
Y
Iwakura
Y
Y
Nakane
A
A
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000276:immunology / Q000502:physiology*; D053938:DNA Fragmentation; D005260:Female; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology; D008089:Listeria monocytogenes / Q000254:growth & development*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma