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

Research Project

Project/Area Number	10671125
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	General surgery
Research Institution	Kumamoto University
Principal Investigator	MITA Seiji KUMAMOTO UNIVERSITY MEDICAL SCHOOL HOSPITAL, SURGERY II, INSTRACTOR, 医学部・附属病院, 助手 (10212234)
Co-Investigator(Kenkyū-buntansha)	OGAWA Michio KUMAMOTO UNIVERSITY MEDICAL SCHOOL, SURGERY II, PROFESSOR, 医学部, 教授 (30028691)
Project Period (FY)	1998 – 1999
Project Status	Completed (Fiscal Year 1999)
Budget Amount *help	¥3,200,000 (Direct Cost: ¥3,200,000) Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000) Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords	CYTOKINE / ORGAN FAILURE / TUMOR-BEARING MOUSE / LPS / colon 26 / colon26
Research Abstract	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.