Interleukin-12 regulates natural killer cell-dependent Propionibacterium acnes-primed, lipopolysaccharide-induced liver injury

Julie A. Margenthaler, Grace Ku, M. Wayne Flye

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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 ofIL-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 6days 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 2days 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.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalHepatology Research
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Endotoxins
  • Interferon-γ
  • Interleukin-12
  • Mononuclear cells
  • Natural killer cells

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