Growth factors in critical illness: Regulation and therapeutic aspects

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 1, Issue 2, 1998, Pages 195-204

  Frost, Robert A ^b   Lang, Charles H ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; GROWTH PROMOTOR; HORMONE; HUMAN GROWTH HORMONE; SOMATOMEDIN C;

ANIMAL; CRITICAL ILLNESS; HUMAN; NUTRITION; PHYSIOLOGY; REVIEW;

ANIMALS; CRITICAL ILLNESS; CYTOKINES; GROWTH SUBSTANCES; HORMONES; HUMAN GROWTH HORMONE; HUMANS; INSULIN-LIKE GROWTH FACTOR I; NUTRITION PHYSIOLOGY;

EID: 0032010176     PISSN: 13631950     EISSN: None     Source Type: Journal    
DOI: 10.1097/00075197-199803000-00010     Document Type: Article

References (75)

1. Laviano A, Renvyle T, Yank ZJ. From laboratory to bedside: new strategies in the treatment of malnutrition in cancer patients. Nutrition 1996; 12:112-122.
2. Wojnar MM, Hawkins WG, Lang CH. Nutritional support of the septic patient. Crit Care Clin 1995; 11:717-733.
3. Deitch EA. Nutritional support of the burn patient. Crit Care Clin 1995; 11:735-750.
4. Sandstrom R, Drott C, Hyltander A, Arfvidsson B, Schersten T, Wickstrom I, Lundholm K. The effect of postoperative intravenous feeding on outcome following major surgery evaluated in a randomized study. Ann Surg 1993; 217:185-195.
5. Sellmeyer DE, Grunfeld C. Endocrine and metabolic disturbances in human immunodeficiency virus infection and the acquired immune deficiency syndrome. Endocr Rev 1996; 17:518-532.
6. Rooyackers OE, Nair KS. Hormonal regulation of human muscle protein metabolism. Ann Rev Nutr 1997; 17:457-485.
7. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995; 16:3-34.
8. Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res 1994; 42:140-144.
9. Zapf J. Total and free IGF serum levels. Eur J Endocrinol 1997; 136:146-147.
10. Bastian SE, Walton PE, Belford DA. Paracellular transport of insulin-like growth factor-I across human umbilical vein endothelial cell monolayers. J Cell Physiol 1997; 170:290-298. The endothelium is the primary barrier separating blood-borne IGF-I from extracellular fluid and tissues. Human umbilical vein endothelial monolayers were grown on microporous membranes in a bichamber system to study transendothelial movement. IGF-I displayed transport similar to that of inulin, a paracellular probe. Additional experiments demonstrated that this transport is not receptor-mediated.
11. Bar RS, Boes M, Clemmons DR, Busby WH, Sandra A, Dake BL, Booth MA. Insulin differentially alters transcapillary movement of intravascular IGFBP-1, IGFBP-2 and endothelial cell IGF binding proteins in the rat heart. Endocrinology 1990; 127:497-499.
12. Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev 1994; 15:80-101.
13. Smith WJ, Underwood LE, Clemmons DR. Effects of caloric or protein restriction on insulin-like growth factor-I and IGF-binding proteins in children and adults. J Clin Endocrinol Metab 1995; 80:443-449.
14. Thissen JP, Pucilowska JB, Underwood LE. Differential regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-1 messenger ribonucleic acids by amino acid availability and growth hormone in rat hepatocyte primary culture. Endocrinology 1994; 134:1570-1576.
15. Zhang J, Whitehead RE, Underwood LE. Effect of fasting on insulin-like growth factor (IGF)-IA and IGF-IB messenger ribonucleic acids and prehormones in rat liver. Endocrinology 1997; 138:3112-3118.
16. 125I-labelled IGF-I in protein restricted rats. Am J Physiol 1992; 262:E406-E411.
17. Yee D, Van Den Berg CL, Kozelsky TW, Kuhn JG, Cox GN. Pharmokinetic profile of recombinant human insulin-like growth factor binding protein-1 in athymic mice. Biomed Pharmacol 1996; 50:154-157.
18. Lee PDK, Conover CA, Powell DR. Regulation and function of insulin-like growth factor binding protein-1. Proc Soc Exp Biol Med 1993; 204:4-29.
19. Bereket A, Wilson TA, Blethen AL, Fan J, Frost RA, Gelato MC, Lang CH. Effect of short-term fasting on free/dissociable insulin-like growth factor-I concentrations in normal human serum. J Clin Endocrinol Metab 1996; 81:4379-4384.
20. Powell DR, Suwanichkul A, Cubbage ML, Depaolis LA, Snuggs MB, Lee PD. Insulin inhibits transcription of the human gene for insulin-like growth factor binding protein-1. J Biol Chem 1991; 266:18868-18876.
21. Ooi GT, Brown DR, Suh DS, Tseng LY, Rechler MM. Cyclohexamide stabilizes insulin-like growth factor binding protein-1 (IGFBP-1) mRNA and inhibits IGFBP-1 transcription in H4II-E rat hepatoma cells. J Biol Chem 1998; 286:16664-16673.
22. Frystyk J, Grofte T, Skjaerbaek C, Orskov H. The effect of oral glucose on serum free insulin-like growth factor-I and -II in healthy adults. J Clin Endorinol Metab 1997; 82:3124-3127.
23. Lewitt MS, Denyer GS, Cooney GJ, Baxter RC. Insulin-like growth factor binding protein-1 modulates blood glucose levels. Endocrinology 1991; 129:2254-2256.
24. Rajkumar K, Krsek M, Dheen ST, Murphy LJ. Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice. J Clin Invest 1996; 98:1818-1825. In transgenic mice that overexpress IGFBP-1 the hypoglycemic response to IGF-I, but not insulin, was attenuated compared with in wild-type mice. There was also an impairment of insulin and IGF-I stimulated glucose uptake and glycogen synthesis in soleus muscle from transgenic mice.
25. Argente J, Caballo N, Barrios V, Munoz MT, Pozo J, Chowen JA, et al. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab 1997; 82:2084-2092.
26. Garibotto G, Barreca A, Russo R, Sofia A, Araghi P, Cesarone A, et al. Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients. J Clin Invest 1997; 99:97-105.
27. Wojnar MM, Fan J, Frost RA, Gelato MC, Lang CH. Alterations in the insulin-like growth factor system in trauma patients. Am J Physiol 1995; 268:R970-R977.
28. Frost RA, Fuhrer J, Mariuz P, Lang CH, Gelato MC. Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system. Clin Endocrinol 1996; 44:501-514.
29. Oster MH, Fielder PJ, Levin N, Cronin MJ. Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition. J Clin Invest 1995; 95:2258-2265.
30. Bang P, Brismar K, Rosenfeld RG, Hall K. Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with non-insulin-dependent diabetes mellitus versus healthy non-obese and obese subjects. J Clin Endocrinol Metab 1994; 78:960-967.
31. Bereket A, Lang CH, Blethen SL, Kaskel FJ, Stewart C, Wilson TA. Growth hormone treatment in growth retarded children with end stage renal failure-effect on free dissociable IGF-I levels. J Pediatr Endocrinol Metab 1997; 10:197-202.
32. Bereket A, Lang CH, Blethen SL, Ng LC, Wilson TA. Insulin treatment normalizes reduced free insulin-like growth factor-I concentrations in diabetic children. Clin Endocrinol 1996; 45:321-326.
33. Juul A, Flyvbjerg A, Frystyk J, Muller J, Skakkebaek NE. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins-1 and -3 and IGFBP-3 protease activity in boys with normal and precocious puberty. Clin Endocrinol 1996; 44:515-523.
34. Voerman HJ, van Schijndel RJMS, Groeneveld ABJ, de Boer H, Nauta JP, Thijs LG. Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens. Metabolism 1992; 41:934-940.
35. Ross R, Miell J, Freeman E, Jones J, Matthews D, Preece M, Buchanan C. Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin Endocrinol 1991; 35:47-54.
36. Vance ML, Hartman ML, Thorner MO. Growth hormone and nutrition. Horm Res 1992; 38:85-88.
37. Lang CH, Pollard V, Traber LD, Traber DL, Frost RA, Gelato MC, Prough DS. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin. Am J Physiol 1997; 273:R371-R378.
38. Peisen JN, McDonnell KJ, Mulroney SE, Lumpkin MD. Endotoxin-induced suppression of the somatotropic axis is mediated by interleukin-1β and corticotropin-releasing factor in the juvenile rat. Endocrinology 1995; 136:3378-3390.
39. Lang CH, Fan J, Cooney R, Vary TC. Interleukin-1 receptor antagonist attenuates sepsis-induced alterations in the insulin-like growth factor system and protein synthesis. Am J Physiol 1996; 270:E430-E437. Data from this study indicate that the decrease in IGF-I in blood, liver and skeletal muscle induced by chronic infection can largely be prevented by treatment with an IL-1 receptor antagonist. These results demonstrate the important role for endogenous IL-1 in mediating changes in IGF-I. Moreover, the sepsis-induced changes in IGF-I content were directly proportional to the in-vivo rate of protein synthesis in the same muscle.
40. Dahn MS, Lange MP, Jacobs LA. Insulin-like growth factor 1 production is inhibited in humans sepsis. Arch Surg 1988; 123:1409-1414.
41. Ross RJ, Chew SL. Acquired growth hormone resistance. Eur J Endocrinol 1995; 132:655-660.
42. Hermansson M, Wickelgren RB, Hammarqvist R, Bjarnason R, Wennstrom I, Wernerman J, et al. Measurement of human growth hormone receptor messenger ribonucleic acid by quantitative polymerase chain reaction-based assay: determination of reduced expression after elective surgery. J Clin Endocrinol Metab 1997; 82:421-428.
43. Rodriguez-Arnao J, Yarwood G, Ferguson C, Miell J, Hinds CJ, Ross RJM. Reduction in circulating IGF-I and hepatic IGF-I mRNA levels after caecal ligation and puncture are associated with differential regulation of hepatic IGF-binding protein-1, -2 and -3 mRNA levels. J Endocrinol 1996; 151:287-292. This study demonstrates that hepatic mRNA abundance for IGFBP-1 and IGFBP-2 are increased, whereas expression of IGFBP-3 mRNA is decreased during infection.
44. Fan J, Li YH, Bagby GJ, Lang CH. Modulation of inflammation-induced changes in insulin-like growth factor (IGF)-I and IGF binding protein-1 by anti-TNF antibody. Shock 1995; 4:21-26.
45. Ghahary A, Fu S, Shen YJ, Shankowsky A, Tredget EE. Differential effects of thermal injury on circulating insulin-like growth factor binding proteins in burn patients. Mol Cell Biochem 1994; 135:171-180.
46. Lang CH, Fan J, Frost RA, Gelato MC, Sakurai Y, Herndon DN, Wolfe RR. Regulation of the insulin-like growth factor system by insulin in burn patients. J Clin Endocrinol Metab 1996; 81:2474-2480. The arteriovenous difference technique is used to demonstrate a net uptake of IGF-I by leg (primarily skeletal muscle) in burn patients.
47. Fan J, Molina PE, Gelato MC, Lang CH. Differential tissue regulation of insulin-like growth factor-I content and binding proteins after endotoxin. Endocrinology 1994; 134:1685-1692.
48. Li YH, Fan J, Lang CH. Differential role of glucocorticoids in mediating endotoxin-induced changes in IGF-I and IGFBP-1. Am J Physiol 1997; 272:R1990-R1997. Using the glucocorticoid receptor antagonist RU486 these investigators were able to demonstrate the role of glucocorticoids in mediating some or all of the changes in IGF-I in the blood, liver and muscle after injection of endotoxin. In contrast, the endotoxin-induced increase in IGFBP-1 appeared to be glucocorticoid-independent.
49. 3IGF-I in pregnant rats. J Endocrinol 1993; 138:327-336.
50. Fan J, Char D, Kolasa AJ, Pan W, Maitra SR, Patlak CS, et al. Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin. Am J Physiol 1995; 269:E33-E42.
51. Yarwood GD, Ross RJ, Medbak S, Coakley J, Hinds CJ. Administration of human recombinant insulin-like growth factor-I in critically ill patients. Crit Care Med 1997; 25:1352-1261.
52. Fan J, Char D, Bagby GJ, Gelato MC, Lang CH. Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor. Am J Physiol 1995; 269:R1204-R1212.
53. Fan J, Wojnar MM, Theodorakis M, Lang CH. Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF binding proteins by interleukin-1. Am J Physiol 1996; 270:R621-R629. Intravenous injection of a nonlethal dose of IL-1β in control animals produced alterations in IGF-I and the IGFBPs that mimicked those observed during infection and traumatic injury. These results, in conjunction with data from previous studies using TNF-α, support the potential importance of cytokines as regulators of the IGF system.
54. Frost RA, Bereket A, Wojnar MM, Lang CH, Gelato MC. Phosphorylation of human insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma. J Clin Endocrinol Metab 1994; 78:1533-1535.
55. Westwood M, Gibson JM, White A. Purification and characterization of the insulin-like growth factor binding protein-1 phosphoisoform found in normal plasma. Endocrinology 1997; 138:1130-1136.
56. Davenport ML, Isley WL, Pucilowska JB, Pemberton LB, Lyman B, Underwood LE, Clemmons DR. Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery. J Clin Endocrinol Metab 1992; 75:590-595.
57. Frost RA, Nachman SA, Lang CH, Gelato MC. Proteolysis of insulin-like growth factor binding protein-3 in human immunodeficiency virus-positive children who fail to thrive. J Clin Endocrinol Metab 1996; 81:2957-2962.
58. Bereket A, Lang CH, Blethen SL, Gelato MC, Fan J, Frost RA, Wilson RA. Effect of insulin on the alterations of growth hormone-IGF axis in children with new onset insulin dependent diabetes mellitus. J Clin Endocrinol Metabol 1995; 80:1312-1317.
59. Lang CH. Mechanism of insulin resistance in infection. In: Pathophysiology of shock, sepsis and organ failure. Schlag G, Redl H (editors). New York: Springer-Verlag; 1993. pp. 609-625.
60. Hall-Angeras M, Angeras U, Zamir O, Hasselgren P-O, Fischer JE. Effect of the glucocorticoid receptor antagonist RU 38486 on muscle protein breakdown in sepsis. Surgery 1991; 109:468-473.
61. Bereket A, Wilson TA, Kolasa AJ, Fan J, Lang CH. Regulation of the insulin-like growth factor system by acute acidosis. Endocrinology 1996; 137:2238-2245.
62. Thissen J-P, Verniers J. Inhibition by interleukin-1β and tumor necrosis factor-α of the insulin-like growth factor I messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture. Endocrinology 1997; 138:1078-1084.
63. Wolf M, Bohm S, Brand M, Kreymann G. Proinflammatory cytokines interleukin 1β and tumor necrosis factor a inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells. Eur J Endocrinol 1996; 135:729-737. This is the first study to demonstrate a direct effect of proinflammatory cytokines on hepatic synthesis and secretion of IGF-I.
64. Samstein B, Hoimes ML, Fan J, Frost RA, Gelato MC, Lang CH. IL-6 stimulation of IGFBP-1 production. Biochem Biophys Res Commun 1996; 228:611-615. This is the first study to demonstrate a direct effect of proinflammatory cytokines on hepatic production of IGFBP-1.
65. Cooney RN, Kimball SR, Vary TC. Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators. Shock 1997; 7:1-16.
66. Clemmons DR. Use of growth hormone and insulin-like growth factor I in catabolism that is induced by negative energy balance. Horm Res 1993; 40:62-67.
67. Jenkins RC, Ross RJM. Growth hormone therapy for protein catabolism. Q J Med 1996; 89:813-819.
68. Vara-Thorbeck R, Ruiz-Requena E, Guerrero-Fernandez JA. Effects of human growth hormone on the catabolic state after surgical trauma. Horm Res 1996; 45:55-60.
69. Koea JB, Breier BH, Douglas RG, Gluckman PD, Shaw JHF. Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis. Br J Surg 1996; 83:196-202. This study provides the most convincing evidence for the beneficial effects of GH in the treatment septic patients. It is noteworthy that GH treatment was significantly more efficacious in patients with moderate protein catabolism, as opposed to in those with severe wasting.
70. Herndon DN, Barrow RE, Kunkel KR, Broemeling L, Rutan RL. Effects of recombinant human growth hormone on donor-site healing in severely burned children. Ann Surg 1990; 212:424-429.
71. Herndon DN, Hawkins HK, Nguyen TT, Pierre E, Cox R, Barrow RE. Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns. Ann Surg 1995; 221:649-659.
72. Meyer NA, Barrow RE, Herndon DN. Combined insulin-like growth factor-1 and growth hormone improves weight loss and wound healing in burned rats. J Trauma 1966; 41:1008-1012.
73. Chen K, Okuma T, Okamura K, Tabira Y, Kaneko H, Miyauchi Y. Insulin-like growth factor-I prevents gut atrophy and maintains intestinal integrity in septic rats. J Parent Enteral Nutr 1995; 19:119-124.
74. Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, et al. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Ann Intern Med 1996; 125:873-882.
75. McNurlan MA, Garlick PJ, Steigbigel RT, DeCristofaro KA, Frost RA, Lang CH, et al. Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J Clin Invest 1997; 100:2125-2132. Basal excretion of 3-methylhistidine was greater in patients with AIDS than in healthy control individuals and human immunodeficiency virus-infected patients without AIDS. Elevated excretion of 3-methylhistidine was observed before the onset of wasting. AIDS patients fail to respond to GH as an anabolic stimulus in muscle, whereas patients who have not developed AIDS respond positively. These results suggest that to be most efficacious GH should be administered before the development of AIDS.