A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis
A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis
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DOI：
10.1038/gt.2008.112
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发表时间：
2008-12
期刊：
影响因子：
5.1
通讯作者：
S. Tohyama;S. Onodera;Harukazu Tohyama;K. Yasuda;Jun Nishihira;Y. Mizue;A. Hamasaka;Riichiro Abe;Yoshikazu Koyama
中科院分区：
文献类型：
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作者：
S. Tohyama;S. Onodera;Harukazu Tohyama;K. Yasuda;Jun Nishihira;Y. Mizue;A. Hamasaka;Riichiro Abe;Yoshikazu Koyama
脓毒症是一种常见且经常致命的疾病，迫切需要新的治疗方法来进一步降低脓毒症引起的死亡率。巨噬细胞移动抑制因子(MIF)在天然免疫和获得性免疫调节中起重要作用，被认为在脓毒症和自身免疫性疾病中起着关键的调节作用。由于MIF缺乏或免疫中和保护小鼠或大鼠免受致死性内毒素休克或其他炎症性疾病的影响，我们检查了针对该分子的DNA疫苗是否也具有保护作用。DNA疫苗可以同时刺激体液免疫和细胞免疫，并已被证明对各种病原体或细胞因子驱动的病理有效。用MIF/破伤风毒素(TTX)DNA疫苗免疫小鼠，然后用脂多糖或盲肠结扎穿孔诱导脓毒症。在两种模型中，MIF/TTX DNA疫苗接种的小鼠与对照疫苗接种的小鼠相比，均可免受脓毒症的致死影响。与对照组相比，MIF/TTX DNA疫苗组小鼠血清肿瘤坏死因子-α蛋白水平显著降低，肺组织肿瘤坏死因子-α、白细胞介素1β、IL-6、巨噬细胞炎性蛋白-2和Toll样受体-4mRNA表达显著降低。因此，MIF/TTX DNA疫苗可用于感染性休克的预防。
Sepsis is a common and frequently fatal condition and there is an urgent need for new therapies that will further reduce sepsis-induced mortality. Macrophage migration inhibitory (MIF) factor is important in the regulation of innate and adaptive immunity and is believed to play a key regulatory role in sepsis and autoimmune disease. As MIF deficiency or immunoneutralization protects mice or rats from fatal endotoxic shock or other inflammatory diseases, we examined whether DNA vaccination against this molecule would also be protective. DNA vaccines can stimulate both humoral and cellular immunity simultaneously and have been shown to be effective against a variety of pathogens or cytokine-driven pathologies. Mice were immunized with a MIF/tetanus toxin (TTX) DNA vaccine and sepsis was then induced by lipopolysaccharide or cecal ligation and puncture. The MIF/TTX DNA-vaccinated mice were protected from the lethal effect of sepsis compared with control-vaccinated mice in both models. Compared with the control-vaccinated mice, the MIF/TTX DNA-vaccinated mice also showed significantly lower serum tumor necrosis factor (TNF)-α protein levels and reduced mRNA expression of TNF-α, interleukin (IL)-1β, IL-6, macrophage inflammatory protein-2 and Toll-like receptor-4 in the lungs. Thus, the MIF/TTX DNA vaccine may be useful for the prophylaxis of septic shock.