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BASIC RESEARCH FOR MECHANISM OF ORGAN FAILURE IN CANCER PATIENTS WITH PARANEOPLASTIC SYNDROME-PROPHYLAXY AND TREATMENT OF PARANEOPLASTIC SYNDROME BY REGULATION OF CYTOKINE PRODUCTION-

副肿瘤综合征癌症患者器官衰竭机制的基础研究-通过调节细胞因子产生预防和治疗副肿瘤综合征-

基本信息

批准号：
10671125
负责人：
MITA Seiji
金额：
$ 2.05万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671125/
关键词：
CYTOKINE ORGAN FAILURE TUMOR-BEARING MOUSE LPS colon 26 colon26

项目摘要

In cancer patients with cachexia and paraneoplastic syndrome, it is important to clarify a role of tumor-producing proinflammatory cytokines, such as TNF-α, IL-1 and IL-6, which also play a critical role in organ dysfunction seen in trauma and infection. In the present study, to explore the effect of lipopolysaccharides(LPS) on the survival, serum cytokine level, ICAM-1 expression, and pathological change of various organ in tumor-bearing mice in which tumor produces IL-6 constitutively.Enzyme-linked-immunosorbent assay and histochemical studies were performed on colon 26 clone5 (c5), low producer of IL-6 or clone20(c20), high producer of IL-6-implanted BALB/c mice treated with LPS. LPS at 20, 50, 115 μg body was administered 7day after inoculation. The sera and organs were collected 2days after LPS administration. 20 or 50 μg of LPS did not shorten the survival period of c5 or c20 bearing mice. A higher survival rate was found in c5 or c20 bearing mice when compared with normal mice given 115 μg LPS. Serum IL-1β increased proportionally with LPS administration in normaland c5-bearing mice groups. Only normal mice showed serum IL-6 rising with LPS administration proportionally. Enhanced expression of ICAM-1 was seen only in normal mice given ll5 μg LPS. These results suggest that the effects of sublethal doses of LPS on the survival were attenuated on IL-6-producing-cancer-bearing mice. It is not likely that modulation of tumor-producing cytokine is effective strategy for prophylaxis of organ dysfunction related to infection in cancer patients with cachexia and paraneoplastic syndrome.

在患有恶病质和副肿瘤综合征的癌症患者中，重要的是澄清产生肿瘤的促炎细胞因子的作用，如肿瘤坏死因子-α、IL-1和IL-6，这些细胞因子在创伤和感染中出现的器官功能障碍中也发挥着关键作用。为探讨脂多糖对IL-6荷瘤小鼠存活时间、血清细胞因子水平、ICAM-1表达及各脏器病理改变的影响，对IL-6低分泌克隆26克隆(C5)和高分泌IL-6克隆BALB/c小鼠(C20)进行了酶联免疫吸附试验和组织化学研究。分别于接种后7天注射20、50、115μg体重的脂多糖。于注射脂多糖后2天采集血清和脏器。20或50μg的脂多糖不能缩短C5或C20荷瘤小鼠的存活时间。与正常小鼠相比，C5或C20荷瘤小鼠的存活率明显提高(P<0.0 5)，注射115GLPS的小鼠存活率明显升高(P<0.0 5)。μg LPS115 mg/kg组小鼠存活率明显高于对照组。正常组和C5荷瘤组小鼠血清IL-1β水平与注射脂多糖成正比。只有正常小鼠血清IL-6水平与注射内毒素成比例升高。细胞间黏附分子-1的表达仅在给予LL5μg脂多糖的正常小鼠中可见增强。这些结果表明，亚致死剂量的内毒素对荷IL-6荷瘤小鼠存活的影响被减弱。肿瘤细胞因子的调节不太可能是预防癌症患者恶病质和副肿瘤综合征患者感染相关器官功能障碍的有效策略。