A pivotal role of IL-12 in Th1-dependent mouse liver injury

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Abstract
Intravenous injection of Proplonibacterium acnes and llpopolysaccharide (LPS) with a 7 day interval caused CD4+ T cell-dependent severe liver injury in the C57BL/6 (H-2b) mouse strain. In contrast, BALB/c (H-2d mice were resistant to P. acnes and LPS-induced liver injury. The different susceptibilities of the two mouse strains to liver injury appeared to be closely correlated with their different abilities to produce IFN-γ after P. acnea priming. Namely, the sensitive C57BL/6 mouse strain produced a significant level of IFN-γ 7–10 days after P. acnes injection, whereas no significant amount of serum IFN-γ was detected in the resistant BALB/c mouse strain. The important role of IFN-γ in liver injury was demonstrated from the finding that In vivo administration of anti-IFN-γ mAb abrogated P. acnes and LPS-induced liver injury in C57BL/6 mice. Moreover, it was demonstrated that In vivo administration of recombinant IL-12, a key cytokine for the induction of IFN-γ, into mice induced P. acnes and LPS-induced liver injury in the resistant BALB/c mouse strain. Conversely, In vivo administration of anti-IL-12 mAb blocked the development of liver injury in the sensitive C57BL/6 mouse strain. Moreover, it was demonstrated that the failure of the induction of liver injury in BALB/c mice appeared to be derived from the lack of expression of IL-12 at the local site of liver in P. acnes-prlmed mice. These results strongly indicated that endogenous IL-12, which stimulates Th 1-dominant cellular immunity and IFN-γ production, may be an essential cytokine on the course of T cell-dependent liver injury.

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