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

在恶病质和副肿瘤综合征的癌症患者中，重要的是要阐明肿瘤产生的促炎细胞因子，如TNF-α，IL-1和IL-6的作用，这也在创伤和感染中观察到的器官功能障碍中发挥关键作用。为探讨脂多糖（LPS）对IL-6分泌型荷瘤小鼠生存期、血清细胞因子水平、ICAM-1表达及各器官病理变化的影响，采用酶联免疫吸附试验（ELISA）和组织化学方法，对IL-6低分泌型结肠癌（colon 26 clone 5，c5）、低分泌型结肠癌（colon 26 clone 20，c20）、低分泌型结肠癌（colon 26 clone 5，c20）、低分泌型结肠癌（colon 26 clone 20，c20）、低分泌型结肠癌（colon 26 clone 5，c20）进行了研究。用LPS处理的IL-6植入的BALB/c小鼠的高产。接种后第7天分别给予20、50、115 μg体重的LPS。注射LPS后2d收集血清和器官。20 μ g或50 μg LPS对c5或c20荷瘤小鼠的生存期无明显缩短作用。与正常小鼠相比，给予115 μ gLPS后，c5或c20荷瘤小鼠的存活率较高。在正常和c5荷瘤小鼠组中，血清IL-1β随LPS给药而成比例增加。只有正常小鼠的血清IL-6与LPS注射成比例地升高。正常小鼠给予115 μg LPS后ICAM-1表达增强。这些结果表明，亚致死剂量的LPS对IL-6产生的荷瘤小鼠的生存的影响减弱。在恶病质和副肿瘤综合征的癌症患者中，调节肿瘤产生细胞因子不太可能是预防与感染相关的器官功能障碍的有效策略。

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.