Abe Kazumichi, Ohira Hiromasa, Kobayashi Hiroko, Rai Tsuyoshi, Saito Hironobu, Takahashi Atsushi, Sato Yukio
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
Fukushima J Med Sci. 2005 Jun;51(1):41-9. doi: 10.5387/fms.51.41.
To investigate the effects of an intradermal injection of oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs on concanavalin A (Con A)-induced hepatitis, an experimental model of immune-mediated hepatitis.
Con A was injected intravenously into Balb/c mice. Twelve hours after Con A challenge, blood and liver samples were obtained. CpG ODN was injected intradermally 48 hours before Con A challenge. The extent of liver injury was assessed by determining serum alanine transaminase (ALT) and by liver histology. Serum levels of cytokines, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4 and IL-5, were measured by enzyme-linked immunosorbent assay.
Co-administration of Con A and CpG ODN significantly increased serum ALT in mice compared with that in the case of administration of Con A alone (10,268 +/- 4,654 and 1,140 +/- 832 IU/1, respectively, p<0.05). In liver histology, mice treated with CpG ODN and Con A showed more extensive midzonal necrosis than did mice treated with Con A alone. These mice also showed significant increases in serum TNF-alpha and IFN-gamma and decrease in serum IL-5.
The results indicate that CpG ODNs aggravate Con A-induced hepatitis by stimulating the production of T-helper-1 (Th1) cytokines, TNF-alpha and IFN-gamma, suggesting that bacterial DNA that contains unmethylated CpG motifs may contribute to the exacerbation of immune-mediated liver injury.
研究皮内注射含未甲基化CpG基序的寡脱氧核苷酸（ODN）对刀豆蛋白A（Con A）诱导的肝炎（一种免疫介导性肝炎的实验模型）的影响。
将Con A静脉注射到Balb/c小鼠体内。Con A攻击12小时后，采集血液和肝脏样本。在Con A攻击前48小时皮内注射CpG ODN。通过测定血清丙氨酸转氨酶（ALT）和肝脏组织学评估肝损伤程度。采用酶联免疫吸附测定法测量包括干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-4和IL-5在内的细胞因子血清水平。
与单独给予Con A相比，Con A与CpG ODN联合给药显著增加了小鼠血清ALT水平（分别为10268±4654和1140±832 IU/L，p<0.05）。在肝脏组织学检查中，用CpG ODN和Con A处理的小鼠比单独用Con A处理的小鼠表现出更广泛的中区坏死。这些小鼠血清TNF-α和IFN-γ也显著增加，血清IL-5降低。
结果表明，CpG ODN通过刺激辅助性T细胞1（Th1）细胞因子TNF-α和IFN-γ的产生加重Con A诱导的肝炎，提示含有未甲基化CpG基序的细菌DNA可能促成免疫介导性肝损伤的加重。
