Ishiwata Y, Yokochi S, Hashimoto H, Ninomiya F, Suzuki T
Developmental Research Department, Sanwa Kagaku Kenkyusho Co. Ltd, Mie, Japan.
Scand J Immunol. 1998 Dec;48(6):605-14. doi: 10.1046/j.1365-3083.1998.00434.x.
Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.
羧乙基锗倍半氧化物（3-氧锗基丙酸聚合物）是一种可激活免疫系统的有机锗化合物。在本研究中，我们调查了羧乙基锗倍半氧化物对刀豆蛋白A（Con A）诱导的T细胞介导的小鼠肝损伤的作用。口服羧乙基锗倍半氧化物可抑制Con A注射后约10小时肝损伤的发展。组织学分析表明，与对照组相比，羧乙基锗倍半氧化物减轻了肝损伤程度，减少了白细胞尤其是CD11b阳性细胞的浸润。CD4阳性细胞的浸润未受影响。肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ对该模型中肝炎的发展至关重要。羧乙基锗倍半氧化物治疗在Con A注射后约10小时诱导了对随后TNF-α产生的显著抑制，而不影响IFN-γ、白细胞介素（IL）-10、IL-4和IL-12的产生。这种对TNF产生的影响与Con A诱导的肝损伤进展后期转氨酶活性的抑制相一致。这些事实表明该化合物影响肝窦中的巨噬细胞（Mphi）功能。因此，将Mphi与肝窦内皮细胞（SEC）一起培养，并确定羧乙基锗倍半氧化物在IFN-γ存在下对TNF-α产生的影响。当用羧乙基锗倍半氧化物处理Mphi时，Mphi与SEC的共培养中TNF-α的产生显著降低。这些结果可能解释了羧乙基锗倍半氧化物抑制Con A诱导的肝损伤的机制。也就是说，羧乙基锗倍半氧化物通过包括减少TNF-α产生在内的机制改善肝炎，而不改变Th1和Th2细胞功能。
