Grant-in-Aid for Scientific Research (C)
|Research Institution||University of Tokyo|
稲葉 毅 東大, 医学部附属病院, 助手 (80272582)
OGURA Makoto Univ. of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (50185568)
古川 聡 東京大学, 医学部・附属病院, 医員
韓 一秀 東京大学, 医学部・附属病院, 医員
不柄 和宏 東京大学, 医学部・附属病院, 医員
井上 知巳 東京大学, 医学部・附属病院, 医員
SAITO Hideaki Univ.of Tokyo, Faculty of Medicine, Assistant professor, 医学部・附属病院, 助教授 (30134555)
深柄 和彦 東京大学, 医学部・附属病院, 医員
FUKATSU Kazuhiko Univ.of Tokyo, Faculty of Medicine
HAN Ilsoo Univ.of Tokyo, Faculty of Medicine
INOUE Tomomi Univ.of Tokyo, Faculty of Medicine
FURUKAWA Satoshi Univ.of Tokyo, Faculty of Medicine
|Project Fiscal Year
1996 – 1997
Completed(Fiscal Year 1997)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥1,400,000 (Direct Cost : ¥1,400,000)
|Keywords||growth hormone / insulin-like growth factor I / surgical insult / immune cell / monocyte / phagocytosis / HLA-DR / reactive oxygen inteymediates / 成長ホルモン / IGF-I / 外科侵襲 / 免疫細胞 / 単球 / 貧食能 / 活性酸素 / 免疫能 / 術後感染症 / インスリン様成長因子- / マクロファージ / 好中球 / mRNA|
Sepsis correlates with immunosupprssion induced by surgical stress and is associated with high mortality after surgery and trauma. Therefore, we investigated the relation between growth hormone(GH)/insulin-like growth factor I(IGF-I)and host immune function, especially in surgical insults. At first, we investigated the relation between surgical stress and immune cell production of insulin-like growth factor I(IGF-I)in autocrine and/or paracrine fashion. However, we did not obtain significant results. Instead, we investigated the effects of exogenous GH and IGF-I on immune function, especially in surgically stressed hosts, and obtained the following findings.
GH enhances CD11b expression on peritoneal exudative neutrophils(PEN_s)in a lethal peritonitis model : Mice were challenged i.p.with 10^8 cfu of E.coli, after 6-days pretreatment with saline(control), GH(4.8mg/kg/day)or IGF-I(24mg/kg/day).GH inceased PEN CD11b expression and PEN numbers, while reducing viable bacterial counts in the
peritoneal lavage fluid.
(2)Preoperative low plasma IGF-I levels are associated with postoperative infectious complications : We measured perioperative plasma levels of GH and IGF-I.Postoperative infectious complications often occurred in patients with preoperative low plasma IGF-I levels.
(3)GH prevents polymorphonuclear neutrophil(PMN)apoptosis in vitro : Peripheral blood PMN_s from healthy human volunteers were incubated with medium(control)or GH(100ng/mL)for 12 hours. Most of PMN_s in the control groups underwent apoptosis. However, GH significantly prevented PMN apoptosis.
(4)GH and IGF-I enhance monocyte function in perioperative patients : Venous blood drawn from patients before and after elective surgery was washed and incubated with medium(Contrl), GH(100ng/mL), or IGF-I(500mg/mL)for 4 hours. GH enhanced postoperative monocyte production of reactive oxygen intermediates. IGF-I enhanced perioperative phagocytosis, TNFalpha production and TNF receptor expression by monocytes. Monocyte HLA-DR expressions decreased postoperatively in all three groups. However, IGF-I prevented the postoperative decrease in monocyte HLA-DR expression which is closely associated with host defense.
These findings suggest that GH and IGF-I enhance immune function and host defense in surgical insults. GH and IGF-I administration may be useful for the prevention and/or management of septic complications associated with surgically stressed states. Less