| Co-Investigator(Kenkyū-buntansha) |
FUKATSU Kazuhiko Faculty of Medicine, Fellow, 医学部(病), 医員 (70323590)
INABA Tsuyoshi Faculty of Medicine, Fellow, 医学部(病), 医員 (80272582)
SUZUKI Kimitaka Faculty of Medicine, Assistant, 医学部(病), 助手 (60221321)
HASHIGUCHI Yojiro Faculty of Medicine, Assistant, 医学部(病), 助手 (60251253)
FUKUSHIMA Ryoji Faculty of Medicine, Assistant, 医学部(病), 助手 (50228897)
井上 知巳 東京大学, 医学部(病), 医員
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We investigated modulation of cytokine production and consequent effects by 1) antecedent nutritional routes, 2) exogenous growth hormone (GH) and insulin-like growth factor I (IGF-I), and 3) administration of a nitric oxide synthase inhibitor (NAME). 4) We also studied the mechanism by which effects of GH on nitrogen metabolism are attenuated in cirrhosis, using northem blot analysis. Method 1) Rats were fed through total parenteral nutrition (TPN) or total enteral nutrition (TEN) for a week, and then challenged i.p.with 3*10^8 E.coli.2) After six days of s.c.treatments with GH (4.8mg/kg/day), IGF-I (24mg/kg/day) or saline, mice were challenged i.p.with 10^8 E.coli.3) One hour after i.p.treatment with NAME (100mg/kg) or saline, mice were challenged i.p.with 10^8 E.coli. 4) Normal and cirrhotic rats received GH (0.8IU/kg/day) or saline for 3 postoperative days after gastrectomy. Results 1) TEN improved survival, increased numbers of peritoneal exudative cells (PEC) and enhanced bacteri
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al clearance with increased local TNF production, while suppressing systemic TNF response, at 2 hours after challenge. 2) GH and IGF-I improved survival, increased PEC numbers and bacterial clearance from peritoneal cavity and liver, while suppressing excessive systemic production of TNF,IL-1 and IL-6, at 6 hours after challenge. 3) Administration of NAME resulted in poor survival times, increases in bacterial numbers in the peritoneal cavity, and an increase in systemic TNF production compared with controls, at four hours after bacterial inoculation. 4) Liver IGF-I-mRNA and plasma IGF-I level were increased in normal rats that received GH,although these values were not increased in cirrhotic rats even if they received GH.Conclusions 1,2) Antecedent enteral nutrition modulates cytokine responses and enhances bacterial clearance after infection, as compared to parenteral nutrition. Exogenous GH and IGF-I also exerts modulatory effects on cytokine production and improves killing of bacteria. These effects of antecedent enteral nutrition, and pretreatment with GH and IGF-I,improve host defense and may prevent the development and progression of postoperative intraperitoneal infection.3) On the other hand, inhibition of nitric oxide production, using NAME,produces detrimental effects in this gram-negative sepsis model. 4) GH administration after surgery does not increase both liver IGF-I-mRNA and plasma IGF-I level in cirrhosis. Therefore, in cirrhosis, exogenous IGF-I may be more effective than GH to improve nitrogen metabolism after surgery. Less
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