• 四川大學(xué)華西醫(yī)院加強(qiáng)醫(yī)療科（成都610041）;

目的　 探討生長(zhǎng)激素（GH）在感染中的作用機(jī)理及安全性。方法　復(fù)習(xí)近年有關(guān)GH在感染中應(yīng)用的研究結(jié)果并進(jìn)行綜述。 結(jié)果　GH在感染患者中有促進(jìn)蛋白合成、增強(qiáng)機(jī)體免疫功能、維護(hù)腸道屏障功能完整性等方面的作用，但部分患者出現(xiàn)GH耐受現(xiàn)象，其安全性有待進(jìn)一步評(píng)估。結(jié)論　GH在感染的治療中有一定的輔助作用，但仍需進(jìn)行深入研究。

引用本文： 王波,康焰. 生長(zhǎng)激素在感染中的應(yīng)用. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006, 13(5): 621-624. doi: 復(fù)制

1. 　Larsen PR, Kronenburg HM, Melmed S, et al. Eds. Williams Textbook of Endocrinology [M]. 10th edition. Philadelphia, PA: Saunders, 2003∶219-225, 1009-1016.
2. 　Onenli-Mungan N, Yildizdas D, Yapicioglu H, et al. Growth hormone and insulin-like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock [J]. J Paediatr Child Health， 2004; 40(4)∶221.
3. 　Lang CH, Pollard V, Fan J, et al. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin [J]. Am J Physiol， 1997; 273(1 Pt 2)∶R371.
4. 　Karinch AM, Pan M, Lin CM, et al. Glutamine metabolism in sepsis and infection [J]. J Nutr， 2001; 131(9 Suppl)∶2535S.
5. 　Vary TC, Dardevet D, Grizard J, et al. Differential regulation of skeletal muscle protein turnover by insulin and IGF-Ⅰ after bacteremia [J]. Am J Physiol， 1998; 275(4 Pt 1)∶E584.
6. 　Chu LW, Lam KS, Tam SC, et al. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients [J]. J Clin Endocrinol Metab， 2001; 86(5)∶1913.
7. 　Koea JB, Breier BH, Douglas RG, et al. Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis [J]. Br J Surg， 1996; 83(2)∶196.
8. 　李維勤， 黎介壽， 許寶華， 等. 重組人GH和全腸外營(yíng)養(yǎng)支持對(duì)腹腔感染患者低白蛋白血癥的治療作用 [J]. 中華外科雜志， 1998； 36(11)∶643.
9. 　Fong Y, Rosenbaum M, Tracey KJ, et al. Recombinant gr-owth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans [J]. Proc Natl Acad Sci USA， 1989; 86(9)∶3371.
10. 　Baroni C. Thymus, peripheral lymphoid tissues and immunological responsiveness of the pituitary dwarf mouse [J]. Experientia， 1967; 23(4)∶282.
11. 　Dantzer R, Kelley KW. Stress and immunity: an integrated view of relationships between the brain and the immune system [J]. Life Sci， 1989; 44(26)∶1995.
12. 　Lantinga van Leeuwen IS, Teske E, van Garderen E, et al. Growth hormone gene expression in normal lymph nodes and lymphomas of the dog [J]. Anticancer Res， 2000; 20(4)∶2371.
13. 　Napolitano LA, Lo JC, Gotway MB, et al. Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone [J]. AIDS， 2002; 16(8)∶1103.
14. 　Pires A, Pido-Lopez J, Moyle G, et al. Enhanced T-cell maturation, differentiation and function in HIV-1-infected individuals after growth hormone and highly active antiretroviral therapy [J]. Antivir Ther， 2004; 9(1)∶67.
15. 　Goodier MR, Imami N, Moyle G, et al. Loss of the CD56 hiCD16-NK cell subset and NK cell interferon-gamma production during antiretroviral therapy for HIV-1: partial recovery by human growth hormone [J]. Clin Exp Immunol， 2003; 134(3)∶470.
16. 　Edwards CK 3rd, Yunger LM, Lorence RM, et al. The pituitary gland is required for protection against lethal effects of Salmonella typhimurium [J]. Proc Natl Acad Sci USA， 1991; 88(6)∶2274.
17. 　Inoue T, Saito H, Fukushima R, et al. Growth hormone and insulinlike growth factor Ⅰ enhance host defense in a murine sepsis model [J]. Arch Surg， 1995; 130(10)∶1115.
18. 　Edwards CK 3rd, Ghiasuddin SM, Yunger LM, et al. In vivo administration of recombinant growth hormone or gamma interferon activities macrophages: enhanced resistance to experimental Salmonella typhimurium infection is correlated with generation of reactive oxygen intermediates [J]. Infect Immun， 1992; 60(6)∶2514.
19. 　Takagi K, Suzuki F, Barrow RE, et al. Growth hormone improves immune function and survival in burned mice infected with herpes simplex virus type 1 [J]. J Surg Res， 1997; 69(1)∶166.
20. 　Balteskard L, Unneberg K, Halvorsen D, et al. Effects of insulin-like growth factor 1 on neutrophil and monocyte functions in normal and septic states [J]. JPEN J Parenter Enteral Nutr， 1998; 22(3)∶127.
21. 　Huang Y, Wang SR, Yi C, et al. Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli [J]. World J Gastroenterol， 2002; 8(6)∶1134.
22. 　Balteskard L, Unneberg K, Mjaaland M, et al. Growth hormone and insulinlike growth factor 1 promote intestinal uptake and hepatic release of glutamine in sepsis [J]. Ann Surg， 1998; 228(1)∶131.
23. 　Jung SE, Youn YK, Lim YS, et al. Combined administration of glutamine and growth hormone synergistically reduces bacterial translocation in sepsis [J]. J Korean Med Sci， 2003; 18(1)∶17.
24. 　Fukushima R, Saito H, Inoue T, et al. Prophylactic treatment with growth hormone and insulin-like growth factor Ⅰ improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis [J]. Burns， 1999; 25(5)∶425.
25. 　Vara-Thorbeck R, Ruiz-Requena E, Guerrero-Fernandez JA.Effects of human growth hormone on the catabolic state after surgical trauma [J]. Horm Res， 1996; 45(1-2)∶55.
26. 　Defalque D, Brandt N, Ketelslegers JM, et al. GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors [J]. Am J Physiol， 1999; 276(3 Pt 1)∶E565.
27. 　Mao Y, Ling PR, Fitzgibbons TP, et al. Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo [J]. Endocrinology， 1999; 140(12)∶5505.
28. 　Hong-Brown LQ, Brown CR, Cooney RN, et al. Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation [J]. Am J Physiol Endocrinol Metab， 2003; 285(1)∶E63.
29. 　Thissen JP, Verniers J. Inhibition by interleukin-1 beta and tumor necrosis factor-alpha of the insulin-like growth factor Ⅰ messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture [J]. Endocrinology， 1997; 138(3)∶1078.
30. 　Colson A, Le Cam A, Maiter D, et al. Potentiation of growth hormone-induced liver suppressors of cytokine signaling messenger ribonucleic acid by cytokines [J]. Endocrinology， 2000; 141(10)∶3687.
31. 　Boisclair YR, Wang J, Shi J, et al. Role of the suppressor of cytokine signaling-3 in mediating the inhibitory effects of interleukin-1beta on the growth hormone-dependent transcription of the acid-labile subunit gene in liver cells [J]. J Biol Chem， 2000; 275(6)∶3841.
32. 　Priego T, Granado M, Ibanez de Caceres I, et al. Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-Ⅰ and IGF-binding protein-3 in rats [J]. J Endocrinol， 2003; 179(1)∶107.
33. 　Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults [J]. N Engl J Med， 1999; 341(11)∶785.
34. 　Moshang T Jr, Rundle AC, Graves DA, et al. Brain tumor recurrence in children treated with growth hormone: the national cooperative growth study experience [J]. J Pediatr， 1996; 128(5 Pt 2)∶S4.
35. 　Bozzola M, Tettoni K, Severi F, et al.Does growth hormone treatment increase chromosomal abnormalities? [J]. Clin Endocrinol (Oxf)， 1997; 47(3)∶363.
36. 　Liu Z, Yu Y, Jiang Y, et al. Growth hormone increases circulating neutrophil activation and provokes lung microvascular injury in septic peritonitis rats [J]. J Surg Res， 2002; 105(2)∶195.
37. 　Liao W, Rudling M, Angelin B. Growth hormone potentiates the in vivo biological activities of endotoxin in the rat [J]. Eur J Clin Invest， 1996; 26(3)∶254.
38. 　Unneberg K, Balteskard L, Mjaaland M, et al.Growth hormone impaired compensation of hemorrhagic shock after trauma and sepsis in swine [J]. J Trauma， 1996; 41(5)∶775.
39. 　Dahn MS, Lange MP. Systemic and splanchnic metabolic response to exogenous human growth hormone [J]. Surgery， 1998; 123(5)∶528.
  1. 1. 　Larsen PR, Kronenburg HM, Melmed S, et al. Eds. Williams Textbook of Endocrinology [M]. 10th edition. Philadelphia, PA: Saunders, 2003∶219-225, 1009-1016.
  2. 2. 　Onenli-Mungan N, Yildizdas D, Yapicioglu H, et al. Growth hormone and insulin-like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock [J]. J Paediatr Child Health， 2004; 40(4)∶221.
  3. 3. 　Lang CH, Pollard V, Fan J, et al. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin [J]. Am J Physiol， 1997; 273(1 Pt 2)∶R371.
  4. 4. 　Karinch AM, Pan M, Lin CM, et al. Glutamine metabolism in sepsis and infection [J]. J Nutr， 2001; 131(9 Suppl)∶2535S.
  5. 5. 　Vary TC, Dardevet D, Grizard J, et al. Differential regulation of skeletal muscle protein turnover by insulin and IGF-Ⅰ after bacteremia [J]. Am J Physiol， 1998; 275(4 Pt 1)∶E584.
  6. 6. 　Chu LW, Lam KS, Tam SC, et al. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients [J]. J Clin Endocrinol Metab， 2001; 86(5)∶1913.
  7. 7. 　Koea JB, Breier BH, Douglas RG, et al. Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis [J]. Br J Surg， 1996; 83(2)∶196.
  8. 8. 　李維勤， 黎介壽， 許寶華， 等. 重組人GH和全腸外營(yíng)養(yǎng)支持對(duì)腹腔感染患者低白蛋白血癥的治療作用 [J]. 中華外科雜志， 1998； 36(11)∶643.
  9. 9. 　Fong Y, Rosenbaum M, Tracey KJ, et al. Recombinant gr-owth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans [J]. Proc Natl Acad Sci USA， 1989; 86(9)∶3371.
  10. 10. 　Baroni C. Thymus, peripheral lymphoid tissues and immunological responsiveness of the pituitary dwarf mouse [J]. Experientia， 1967; 23(4)∶282.
  11. 11. 　Dantzer R, Kelley KW. Stress and immunity: an integrated view of relationships between the brain and the immune system [J]. Life Sci， 1989; 44(26)∶1995.
  12. 12. 　Lantinga van Leeuwen IS, Teske E, van Garderen E, et al. Growth hormone gene expression in normal lymph nodes and lymphomas of the dog [J]. Anticancer Res， 2000; 20(4)∶2371.
  13. 13. 　Napolitano LA, Lo JC, Gotway MB, et al. Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone [J]. AIDS， 2002; 16(8)∶1103.
  14. 14. 　Pires A, Pido-Lopez J, Moyle G, et al. Enhanced T-cell maturation, differentiation and function in HIV-1-infected individuals after growth hormone and highly active antiretroviral therapy [J]. Antivir Ther， 2004; 9(1)∶67.
  15. 15. 　Goodier MR, Imami N, Moyle G, et al. Loss of the CD56 hiCD16-NK cell subset and NK cell interferon-gamma production during antiretroviral therapy for HIV-1: partial recovery by human growth hormone [J]. Clin Exp Immunol， 2003; 134(3)∶470.
  16. 16. 　Edwards CK 3rd, Yunger LM, Lorence RM, et al. The pituitary gland is required for protection against lethal effects of Salmonella typhimurium [J]. Proc Natl Acad Sci USA， 1991; 88(6)∶2274.
  17. 17. 　Inoue T, Saito H, Fukushima R, et al. Growth hormone and insulinlike growth factor Ⅰ enhance host defense in a murine sepsis model [J]. Arch Surg， 1995; 130(10)∶1115.
  18. 18. 　Edwards CK 3rd, Ghiasuddin SM, Yunger LM, et al. In vivo administration of recombinant growth hormone or gamma interferon activities macrophages: enhanced resistance to experimental Salmonella typhimurium infection is correlated with generation of reactive oxygen intermediates [J]. Infect Immun， 1992; 60(6)∶2514.
  19. 19. 　Takagi K, Suzuki F, Barrow RE, et al. Growth hormone improves immune function and survival in burned mice infected with herpes simplex virus type 1 [J]. J Surg Res， 1997; 69(1)∶166.
  20. 20. 　Balteskard L, Unneberg K, Halvorsen D, et al. Effects of insulin-like growth factor 1 on neutrophil and monocyte functions in normal and septic states [J]. JPEN J Parenter Enteral Nutr， 1998; 22(3)∶127.
  21. 21. 　Huang Y, Wang SR, Yi C, et al. Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli [J]. World J Gastroenterol， 2002; 8(6)∶1134.
  22. 22. 　Balteskard L, Unneberg K, Mjaaland M, et al. Growth hormone and insulinlike growth factor 1 promote intestinal uptake and hepatic release of glutamine in sepsis [J]. Ann Surg， 1998; 228(1)∶131.
  23. 23. 　Jung SE, Youn YK, Lim YS, et al. Combined administration of glutamine and growth hormone synergistically reduces bacterial translocation in sepsis [J]. J Korean Med Sci， 2003; 18(1)∶17.
  24. 24. 　Fukushima R, Saito H, Inoue T, et al. Prophylactic treatment with growth hormone and insulin-like growth factor Ⅰ improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis [J]. Burns， 1999; 25(5)∶425.
  25. 25. 　Vara-Thorbeck R, Ruiz-Requena E, Guerrero-Fernandez JA.Effects of human growth hormone on the catabolic state after surgical trauma [J]. Horm Res， 1996; 45(1-2)∶55.
  26. 26. 　Defalque D, Brandt N, Ketelslegers JM, et al. GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors [J]. Am J Physiol， 1999; 276(3 Pt 1)∶E565.
  27. 27. 　Mao Y, Ling PR, Fitzgibbons TP, et al. Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo [J]. Endocrinology， 1999; 140(12)∶5505.
  28. 28. 　Hong-Brown LQ, Brown CR, Cooney RN, et al. Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation [J]. Am J Physiol Endocrinol Metab， 2003; 285(1)∶E63.
  29. 29. 　Thissen JP, Verniers J. Inhibition by interleukin-1 beta and tumor necrosis factor-alpha of the insulin-like growth factor Ⅰ messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture [J]. Endocrinology， 1997; 138(3)∶1078.
  30. 30. 　Colson A, Le Cam A, Maiter D, et al. Potentiation of growth hormone-induced liver suppressors of cytokine signaling messenger ribonucleic acid by cytokines [J]. Endocrinology， 2000; 141(10)∶3687.
  31. 31. 　Boisclair YR, Wang J, Shi J, et al. Role of the suppressor of cytokine signaling-3 in mediating the inhibitory effects of interleukin-1beta on the growth hormone-dependent transcription of the acid-labile subunit gene in liver cells [J]. J Biol Chem， 2000; 275(6)∶3841.
  32. 32. 　Priego T, Granado M, Ibanez de Caceres I, et al. Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-Ⅰ and IGF-binding protein-3 in rats [J]. J Endocrinol， 2003; 179(1)∶107.
  33. 33. 　Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults [J]. N Engl J Med， 1999; 341(11)∶785.
  34. 34. 　Moshang T Jr, Rundle AC, Graves DA, et al. Brain tumor recurrence in children treated with growth hormone: the national cooperative growth study experience [J]. J Pediatr， 1996; 128(5 Pt 2)∶S4.
  35. 35. 　Bozzola M, Tettoni K, Severi F, et al.Does growth hormone treatment increase chromosomal abnormalities? [J]. Clin Endocrinol (Oxf)， 1997; 47(3)∶363.
  36. 36. 　Liu Z, Yu Y, Jiang Y, et al. Growth hormone increases circulating neutrophil activation and provokes lung microvascular injury in septic peritonitis rats [J]. J Surg Res， 2002; 105(2)∶195.
  37. 37. 　Liao W, Rudling M, Angelin B. Growth hormone potentiates the in vivo biological activities of endotoxin in the rat [J]. Eur J Clin Invest， 1996; 26(3)∶254.
  38. 38. 　Unneberg K, Balteskard L, Mjaaland M, et al.Growth hormone impaired compensation of hemorrhagic shock after trauma and sepsis in swine [J]. J Trauma， 1996; 41(5)∶775.
  39. 39. 　Dahn MS, Lange MP. Systemic and splanchnic metabolic response to exogenous human growth hormone [J]. Surgery， 1998; 123(5)∶528.