Suzuki A, Takahashi T, Okuno Y, Seko S, Fukuda Y, Nakamura K, Fukumoto M, Konaka Y, Imura H
Second Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Am J Med. 1993 Feb;94(2):125-32. doi: 10.1016/0002-9343(93)90173-m.
We have demonstrated that colony-stimulating factor (CSF)-producing tumor cell lines produce not only CSF but also interleukin-1 (IL-1) and interleukin-6 (IL-6). Clinically, we have observed that patients bearing such tumors present with liver dysfunction and fever in addition to marked leukocytosis. The purpose of this study was to determine whether or not the liver damage was specifically related to CSF-producing tumors.
Clinicopathologic examinations were performed in six autopsied patients with CSF-producing tumors. We also transplanted two tumor cell lines (KHC287 and CHU-2), which produce granulocyte (G)-CSF, IL-1, and IL-6, to nude mice.
Of the six patients, five had G-CSF- and one had granulocyte/macrophage (GM)-CSF-producing tumors. IL-1 and IL-6 concentrations in plasma or culture supernatant were elevated in these patients. Biochemical examinations revealed high serum enzyme levels of the biliary system in contrast to normal or slight increases in transaminase levels in all patients studied. Serum direct bilirubin was elevated in five of the six patients. Three common pathologic changes of the liver were found: (1) focal necrosis associated with neutrophil infiltration in the centrilobular zones, (2) fibrous change and enlargement of the portal area associated with neutrophil infiltration, and (3) intrahepatic cholestasis. The same pathologic changes, except for cholestasis, were reproduced in the liver of mice transplanted with KHC287 or CHU-2.
These results indicate that patients with CSF-producing tumors have characteristic liver damage, and suggest a new paraneoplastic syndrome of leukocytosis and liver damage.
我们已经证明，产生集落刺激因子（CSF）的肿瘤细胞系不仅产生CSF，还产生白细胞介素-1（IL-1）和白细胞介素-6（IL-6）。临床上，我们观察到患有此类肿瘤的患者除了白细胞显著增多外，还伴有肝功能障碍和发热。本研究的目的是确定肝损伤是否与产生CSF的肿瘤有特定关联。
对6例患有产生CSF肿瘤的尸检患者进行了临床病理检查。我们还将两种产生粒细胞（G）-CSF、IL-1和IL-6的肿瘤细胞系（KHC287和CHU-2）移植到裸鼠体内。
6例患者中，5例患有产生G-CSF的肿瘤，1例患有产生粒细胞/巨噬细胞（GM）-CSF的肿瘤。这些患者血浆或培养上清液中的IL-1和IL-6浓度升高。生化检查显示，与所有研究患者转氨酶水平正常或略有升高形成对比的是，胆汁系统的血清酶水平较高。6例患者中有5例血清直接胆红素升高。发现肝脏有三种常见的病理变化：（1）小叶中心区局灶性坏死伴中性粒细胞浸润；（2）门管区纤维性改变和扩大伴中性粒细胞浸润；（3）肝内胆汁淤积。在用KHC287或CHU-2移植的小鼠肝脏中再现了相同的病理变化，除了胆汁淤积。
这些结果表明，患有产生CSF肿瘤的患者有特征性肝损伤，并提示一种新的白细胞增多和肝损伤的副肿瘤综合征。
