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Interleukin‐12 regulates natural killer cell‐dependent Propionibacterium acnes ‐primed, lipopolysaccharide‐induced liver injury
Author(s) -
Margenthaler Julie A.,
Ku Grace,
Flye M. Wayne
Publication year - 2008
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00214.x
Subject(s) - propionibacterium acnes , cytokine , peripheral blood mononuclear cell , lipopolysaccharide , liver injury , interleukin , monoclonal antibody , immunology , natural killer cell , biology , medicine , antibody , in vitro , pharmacology , cytotoxic t cell , genetics , bacteria , biochemistry
Aim: Interleukin (IL)‐12, produced primarily by macrophage/monocytes, modulates mature T and natural killer (NK) cell functions, including cytotoxicity and cytokine production. Methods: To determine the role of IL‐12 in Propionibacterium acnes ( P. acnes )‐primed, lipopolysaccharide (LPS)‐induced liver injury, mice were injected with an anti‐IL‐12 monoclonal antibody (mAb) 1 and 2 days before P. acnes injection (day 0) or 5 and 6 days before LPS challenge (day 7). The survival rates, plasma cytokine levels, and liver mononuclear cell phenotypes were evaluated for the mice treated with and without anti‐IL‐12 mAb. Results: The observed mortality with P. acnes ‐primed, LPS‐induced liver injury in C57BL/6 (B6) mice was 100%, but was reduced to 0% in interferon (IFN)‐γ receptor‐deficient mice and B6 mice treated with anti‐IL‐12 mAb on 1 and 2 days before P. acnes exposure (day 0). The plasma IFN‐γ levels weresignificantly lower ( P < 0.05), and significantly less (∼90% reduction) hepatic infiltrating mononuclear and NK1.1 cells were also found in the IL‐12 mAb‐treated, P. acnes ‐primed mice. The plasma cytokine levels after LPS challenge and in vitro cytokine release by liver mononuclear cells were significantly lower ( P < 0.05) in the mice treated with anti‐IL‐12 mAb prior to P. acnes exposure. The in vivo administration of anti‐NK1.1 mAb also improved survival in this liver injury model. Conclusion: IL‐12‐regulated IFN‐γ production is crucial during the priming phase by P. acnes, but not at the time of the subsequent LPS challenge. NK1.1 + CD3 ‐ CD4 ‐ NK or NK1.1 + CD3 + CD4 ‐ NKT cells are important in this model of liver injury.