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Strain difference in the induction of T‐cell activation–associated, interferon gamma–dependent hepatic injury in mice
Author(s) -
Mizuhara Hidekazu,
Kuno Masako,
Seki Nobuo,
Yu WenGong,
Yamaoka Makiko,
Yamashita Masakatsu,
Ogawa Toshikazu,
Kaneda Kenji,
Fujii Takashi,
Senoh Hachiro,
Fujiwara Hiromi
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270227
Subject(s) - concanavalin a , medicine , spleen , tumor necrosis factor alpha , c57bl/6 , endocrinology , microbiology and biotechnology , interferon , lymphokine , ratón , cytokine , interferon gamma , stimulation , strain (injury) , liver injury , chemistry , biology , immunology , in vitro , immune system , biochemistry
A single intravenous injection of concanavalin A (Con A) induces T‐cell activation–associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A–induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T‐cell–derived lymphokines (interferon gamma [IFN‐γ], tumor necrosis factor α [TNF‐α], and interleukin‐2 [IL‐2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF‐α and IL‐2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN‐γ production in C57BL/6 mice. RNA from livers of Con A–treated C57BL/6 mice exhibited lower levels of IFN‐γ mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti–IFN‐γ monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN‐γ exhibited higher IFN‐γ responsiveness as exemplified by the intrahepatic expression of an IFN‐γ–inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN‐γ produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN‐γ–dependent hepatic injury.