Mediators for the aggravation of acute pancreatitis-the role of cytokies and activated neutrophils
Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kumamoto University|
OGAWA Michio Department of Surgery II Professor, 医学部, 教授 (30028691)
BEPPU Toru Kumamoto University Department of Surgery II Staff surgeon, 医学部・付属病院, 医員
EAGAMI Hiroshi Kumamoto University Department of Surgery II Insructor, 医学部, 助手 (00264284)
KATAFUCHI Shigeru Kumamoto University Department of Surgery II Insructor, 医学部, 助手 (50233747)
MORI Katsutaka Kumamoto University College of Medical Science Professor, 医療短期大学部, 教授 (10040213)
緒方 健一 熊本大学, 医学部附属病院, 医員
池井 聰 熊本大学, 医学部, 講師 (90136705)
|Project Period (FY)
1993 – 1994
Completed(Fiscal Year 1994)
|Budget Amount *help
¥6,900,000 (Direct Cost : ¥6,900,000)
Fiscal Year 1994 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1993 : ¥5,900,000 (Direct Cost : ¥5,900,000)
|Keywords||acute pancreatitis / cytokine / TNF-alpha / activated neutrophils / CINC / LPS / multiple organ failures / ARDS / 好中球 / セルレイン / エンドトキシン|
The present sudy was undertaken to investigate the roles of cytokines and activated neutrophils on the aggravation of cerulein-induced acute pancreatitis in rats. These mediators may induce multiple organ failures.
1.In vitro tumot necrosis factor-alpha (TNF-alpha) production in response to lipopolysaccharide (LPS) by peritoneal macrophages taken from cerulein-induced pancretitis rats was signifcantly enhanced compared to that odserved in naive controls.
2.Pancreatitis of non-pancreatitis rats were injected intraperitoneally with LPS as a septic challenge.
(1) Serum levels of TNF-alpha in pancreatitis rats with LPS were significantly higher than those in non-pancreatitis rats with LPS.
(2) In vitro TNF-alpha production by bronchoalveolar macrophages obtained from pancreatitis rats with LPS were significantly enhaced compared to those in non-pancreatitis rats with LPS.
(3) Neutrophil accumulation to the lungs was increased in pancreatitis rats with LPS compared to that in non-pancreatitis ra
ts with LPS.
(4) In addition, myeloperoxidase activity in the lung was significantly increased in pancreatitis rats with LPS.
(5) Superoxide production of brochoalveolar macrophages determined by in situ nitro blue terazolium (NBT) method was also enhanced in pancreatis rats with LPS.
(6) Liver dysfucntinos were predominantly noted in pancreatitis rats with LPS, serologically and histologically.
The survival rates during 24 hours in pancreatitis rats with LPS was significantly shorter than those in non-pancreatitis rats with LPS.
The administration of protease inhibitors tends to decrease cytokine production and liver dysfunction in pancreatitis rats with LPS.
Thus, hypercytokinemia and remote organ failures were encountered in pancreatitis rats when endotoxemia was involved. In cerulein-induced acute pancreatitis, macrophages could be primed and activated to release a large amount of cytokines when LPS was administared as the second attack. As a result, neutrphils accumulated into the remote organs leading to the tissue destruction. The administation of protease inhibitors trends to ameliorate these organ faulires. However, futrther experiments were required. Less
Research Output (32results)