Immunosuppression in the livers of mice with obstructive jaundice participates in their susceptibility to bacterial infection and tumor metastasis.
Although patients with obstructive jaundice are susceptible to bacterial infections and cancers, the mechanisms remain to be elucidated. In the present study, liver mononuclear cells (MNCs) of bile duct-ligated (BDL) mice were immunologically assessed. Liver natural killer T cells were greatly decreased within 24 h after BDL. Upon injection of Escherichia coli (E. coli; 10 colony-forming units) at 7 days after the procedure, all BDL mice had died, but no sham mice died. Consistently, an overgrowth of E. coli was seen in the livers of BDL mice. Although the serum IL-12 and IL-18 levels after E. coli challenge in BDL mice were higher than those in sham mice, the IFN-gamma level was greatly suppressed. However, exogenous IFN-gamma injection significantly increased BDL mouse survival after E. coli challenge. Furthermore, liver MNC of BDL mice exhibited a lower cytotoxic activity against tumors, and BDL mice intravenously injected with liver metastatic EL-4 cells showed markedly increased EL-4 metastases. The total bile acids, as well as the bile acid fractions, increased in the sera and liver. IFN-gamma production by liver MNC from normal mice stimulated with LPS in vitro was inhibited by the addition of bile acids, whereas, conversely, the production of IL-12 and IL-18 increased. In conclusion, liver natural killer T cells were diminished in BDL mice, and the function of liver MNC (IFN-gamma production) was also impaired presumably due to increased bile acids. This may partly explain the increased susceptibility of BDL mice to bacterial infections and tumor metastasis.
Kawarabayashi
Nobuaki
N
Department of Surgery, National Defense Medical College, Tokorozawa, Japan.
Seki
Shuhji
S
Hatsuse
Kazuo
K
Kinoshita
Manabu
M
Takigawa
Toshimichi
T
Tsujimoto
Hironori
H
Kawabata
Toshinobu
T
Nakashima
Hiroyuki
H
Shono
Satoshi
S
Mochizuki
Hidetaka
H
D000818:Animals; D001424:Bacterial Infections; D001647:Bile Acids and Salts / Q000009:adverse effects / Q000097:blood; D004198:Disease Susceptibility / Q000276:immunology; D004927:Escherichia coli Infections / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12; D020382:Interleukin-18; D041781:Jaundice, Obstructive / Q000150:complications / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology
D001647:Bile Acids and Salts; D020382:Interleukin-18; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma