INTERLEUKIN-12 IS PRODUCED IN-VIVO DURING ENDOTOXEMIA AND STIMULATES SYNTHESIS OF GAMMA-INTERFERON
INTERLEUKIN-12 IS PRODUCED IN-VIVO DURING ENDOTOXEMIA AND STIMULATES SYNTHESIS OF GAMMA-INTERFERON
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DOI：
10.1128/iai.62.10.4244-4249.1994
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发表时间：
1994-10-01
影响因子：
3.1
通讯作者：
SCHOENHAUT, DS
中科院分区：
文献类型：
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作者：
HEINZEL, FP;RERKO, RM;SCHOENHAUT, DS
γ干扰素（IFN-γ）是响应循环脂多糖（LPS）产生的，并有助于内毒素休克的致死性。为了解决体内IFN-γ产生的细胞来源，在内毒素注射后5小时，从C57 BL/6小鼠脾磁性纯化T细胞和B细胞。IFN-γ RNA在脾CD 4（+）和CD 8（+）T细胞以及含有34%NK 1.1（+）自然杀伤（NK）细胞的T细胞和B细胞耗竭的脾细胞群中丰富。由于白细胞介素12（IL-12）是一种已知的诱导因子IFN-γ的合成培养的T细胞和NK细胞，我们研究了IL-12是否可能参与IFN-γ的释放在内毒素血症。C57 BL/6小鼠脾组织中IL-12 p40亚单位mRNA在LPS注射后2 h显著增加，而p35 IL-12 mRNA在各时间点均呈组成型表达。在LPS注射后2至4 h，在小鼠血清中检测到生物活性IL-12（p70异源二聚体）。使用p40亚基特异性酶联免疫吸附试验获得了类似的结果。内毒素不敏感的C3 H/HeJ小鼠在这些时间产生的IL-12 p70和IFN-γ比内毒素敏感的C3 H/HeOuJ小鼠少三倍。在三个独立的实验中，用多克隆抗小鼠IL-12抗体预处理小鼠使LPS后6小时存在的IFN-γ水平降低近六倍。这些研究支持IL-12在内毒素血症期间作为IFN-γ释放的近端刺激物的作用。
Gamma interferon (IFN-gamma) is produced in response to circulating lipopolysaccharide (LPS) and contributes to the lethality of endotoxic shock. To address the cellular source of IFN-gamma production in vivo, T cells and B cells were magnetically purified from C57BL/6 mouse spleens 5 h following endotoxin injection. IFN-gamma RNA was abundant in splenic CD4(+) and CD8(+) T cells and in a T- and B-cell-depleted population of splenocytes containing 34% NK1.1(+) natural killer (NK) cells. Because interleukin 12 (IL-12) is a known inducer of IFN-gamma synthesis by cultured T cells and NK cells, we examined whether IL-12 might be involved in IFN-gamma release during endotoxemia. mRNA encoding the p40 subunit of IL-12 increased markedly in the spleens of C57BL/6 mice at 2 h after LPS injection, whereas p35 IL-12 mRNA was constitutively expressed at ail times. Bioactive IL-12 (p70 heterodimer) was detected in mouse serum at 2 to 4 h after LPS injection. Similar results were obtained using a p40 subunit-specific enzyme-linked immunosorbent assay. Endotoxin-insensitive C3H/HeJ mice generated threefold less IL-12 p70 and IFN-gamma at these times than endotoxin-sensitive C3H/HeOuJ mice. Pretreatment of mice with polyclonal anti-mouse IL-12 antibody reduced IFN-gamma levels present at 6 h post-LPS nearly sixfold in three separate experiments. These studies support a role for IL-12 as a proximal stimulator of IFN-gamma release during endotoxemia.