Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Hepatol Res. 2008;38(2):183-93. doi: 10.1111/j.1872-034X.2007.00214.x.
Interleukin (IL)-12, produced primarily by macrophage/monocytes, modulates mature T and natural killer (NK) cell functions, including cytotoxicity and cytokine production.
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.
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)-gamma 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-gamma levels weresignificantly lower (P < 0.05), and significantly less ( approximately 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.
IL-12-regulated IFN-gamma 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.
白细胞介素（IL）-12 主要由巨噬细胞/单核细胞产生，调节成熟 T 细胞和自然杀伤（NK）细胞的功能，包括细胞毒性和细胞因子产生。
为了确定 IL-12 在痤疮丙酸杆菌（P. acnes）引发的脂多糖（LPS）诱导的肝损伤中的作用，在 P. acnes 注射前 1 天和 2 天（第 0 天）或 LPS 挑战前 5 天和 6 天（第 7 天）给小鼠注射抗 IL-12 单克隆抗体（mAb）。评估用和未用抗 IL-12 mAb 治疗的小鼠的存活率、血浆细胞因子水平和肝单核细胞表型。
在 C57BL/6（B6）小鼠中，P. acnes 引发的 LPS 诱导的肝损伤的死亡率为 100%，但在干扰素（IFN）-γ受体缺陷小鼠和在 P. acnes 暴露前 1 天和 2 天（第 0 天）用抗 IL-12 mAb 治疗的 B6 小鼠中降至 0%。血浆 IFN-γ水平显著降低（P < 0.05），并且在 IL-12 mAb 治疗的 P. acnes 引发的小鼠中也发现了显著减少的（约 90%减少）肝浸润单核细胞和 NK1.1 细胞。在 P. acnes 暴露前用抗 IL-12 mAb 治疗的小鼠，在 LPS 挑战后的血浆细胞因子水平和肝单核细胞的体外细胞因子释放均显著降低（P < 0.05）。体内给予抗 NK1.1 mAb 也改善了该肝损伤模型的存活率。
在 P. acnes 的引发阶段，IL-12 调节的 IFN-γ产生至关重要，但在随后的 LPS 挑战时则不重要。在该肝损伤模型中，NK1.1（+）CD3（-）CD4（-）NK 或 NK1.1（+）CD3（+）CD4（-）NKT 细胞很重要。
