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

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