|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1999 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1998 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
(1) The significance of neutrophils in tumor-bearing rats was investigated using monoclonal antibody (RP3) which reduced rat neutrophils selectively. G-CSF, which induced neutrophiis from bone marrow, and/or OK-432, which induced peripheral blood neutrophils and augmented its activity, were used. G-CSF enhanced the tumor growth at an early period after tumor inoculation, while OK-432 reduced it. It is suggested that neutrophils might show biphasic activity against tumor growth according to the tumor-bearing period. Thus, in the early stage of cancer, it may be cytotoxic, while at the end stage of cancer, it may be suppressive.
(2) The peripheral blood neutrophfis of patients with advanced gastric or colorectal cancers increased remarkably, and both their phagocytic activity and superoxide production per neutriohils showed lower values than those of healthy volunteers. The serum interleukin (IL)-6, IL-8 and IL-10 levels of the patients were higher than those of healthy volunteers.
(3) In rat peritonitis model produced by cecal legation and puncture (CLP), the survival rate was decreased with the administration of neutrophil-depleting antibody, RP3, before or 8 hours after CLP, whereas it showed no change with administration 12, 18, 24 or 48 hours after CLP. We also conducted a study to asses cytokine (IL-6, IL-10, TNF-α) production in peripheral blood cells of the CLP model. Heparinized whole blood cells of rats were incubated with LPS for 24 hours. IL-6 or IL-10 production was decreased up to a peak 12-24 hours after CLP. TNF-α could be produced before CLP, decreased after 6 hours and then increased up to 24 hours.