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. 1991 Aug;32(8):913–917. doi: 10.1136/gut.32.8.913

Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease.

S H Murch 1, V A Lamkin 1, M O Savage 1, J A Walker-Smith 1, T T MacDonald 1
PMCID: PMC1378961  PMID: 1885073

Abstract

Serum tumour necrosis factor alpha (TNF alpha) concentrations were measured by enzyme linked immunoadsorbent assay in 31 normal children and during 65 episodes of clinical remission and 54 episodes of relapse in 92 children with chronic inflammatory bowel disease. An appreciable rise in TNF alpha was found only in children in relapse of ulcerative colitis and colonic Crohn's disease. The group of children with small bowel Crohn's disease in relapse did not show increases of TNF alpha above control concentrations, despite an equivalent rise in disease indices. Height velocity was depressed in children with relapse of large bowel Crohn's disease and ulcerative colitis compared with the equivalent condition in remission. The impairment of growth velocity was significantly greater in relapse of large bowel Crohn's disease and ulcerative colitis than in small bowel Crohn's disease alone, although for the subgroups in stage 1 puberty (prepubertal) the differences were not significant. Inadequate growth in chronic inflammatory bowel disease is currently ascribed to inadequate nutrition and TNF alpha may contribute to this through its cachexia inducing effects. It may, in addition, diminish pituitary growth hormone release. These results suggest that production of TNF alpha may be associated with growth failure in relapse of colonic inflammatory bowel disease.

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Selected References

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  1. Aiges H., Markowitz J., Rosa J., Daum F. Home nocturnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn's disease. Gastroenterology. 1989 Oct;97(4):905–910. doi: 10.1016/0016-5085(89)91496-0. [DOI] [PubMed] [Google Scholar]
  2. Alperstein G., Daum F., Fisher S. E., Aiges H., Markowitz J., Becker J., So H., Schwartz D., Silverberg M., Schneider K. Linear growth following surgery in children and adolescents with Crohn's disease: relationship to pubertal status. J Pediatr Surg. 1985 Apr;20(2):129–133. doi: 10.1016/s0022-3468(85)80284-0. [DOI] [PubMed] [Google Scholar]
  3. Amarnath R. P., Fleming C. R., Perrault J. Home parenteral nutrition in chronic intestinal diseases: its effect on growth and development. J Pediatr Gastroenterol Nutr. 1987 Jan-Feb;6(1):89–95. doi: 10.1097/00005176-198701000-00016. [DOI] [PubMed] [Google Scholar]
  4. Balkwill F., Osborne R., Burke F., Naylor S., Talbot D., Durbin H., Tavernier J., Fiers W. Evidence for tumour necrosis factor/cachectin production in cancer. Lancet. 1987 Nov 28;2(8570):1229–1232. doi: 10.1016/s0140-6736(87)91850-2. [DOI] [PubMed] [Google Scholar]
  5. Belli D. C., Seidman E., Bouthillier L., Weber A. M., Roy C. C., Pletincx M., Beaulieu M., Morin C. L. Chronic intermittent elemental diet improves growth failure in children with Crohn's disease. Gastroenterology. 1988 Mar;94(3):603–610. doi: 10.1016/0016-5085(88)90230-2. [DOI] [PubMed] [Google Scholar]
  6. Brenner D. A., Buck M., Feitelberg S. P., Chojkier M. Tumor necrosis factor-alpha inhibits albumin gene expression in a murine model of cachexia. J Clin Invest. 1990 Jan;85(1):248–255. doi: 10.1172/JCI114419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chong S. K., Grossman A., Walker-Smith J. A., Rees L. H. Endocrine dysfunction in children with Crohn's disease. J Pediatr Gastroenterol Nutr. 1984 Sep;3(4):529–534. doi: 10.1097/00005176-198409000-00009. [DOI] [PubMed] [Google Scholar]
  8. Choy M. Y., Walker-Smith J. A., Williams C. B., MacDonald T. T. Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. Gut. 1990 Dec;31(12):1365–1370. doi: 10.1136/gut.31.12.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark I. A., Cowden W. B., Butcher G. A., Hunt N. H. Possible roles of tumor necrosis factor in the pathology of malaria. Am J Pathol. 1987 Oct;129(1):192–199. [PMC free article] [PubMed] [Google Scholar]
  10. Davies G., Evans C. M., Shand W. S., Walker-Smith J. A. Surgery for Crohn's disease in childhood: influence of site of disease and operative procedure on outcome. Br J Surg. 1990 Aug;77(8):891–894. doi: 10.1002/bjs.1800770816. [DOI] [PubMed] [Google Scholar]
  11. Evans D. A., Jacobs D. O., Revhaug A., Wilmore D. W. The effects of tumor necrosis factor and their selective inhibition by ibuprofen. Ann Surg. 1989 Mar;209(3):312–321. doi: 10.1097/00000658-198903000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Evans M., Walker-Smith J. Recording growth and development in children with inflammatory bowel disease. BMJ. 1989 May 13;298(6683):1312–1313. doi: 10.1136/bmj.298.6683.1312-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans R. D. Gastric effects of cytokines. Anaesthesia. 1989 Jun;44(6):518–518. doi: 10.1111/j.1365-2044.1989.tb11387.x. [DOI] [PubMed] [Google Scholar]
  14. Farthing M. J., Campbell C. A., Walker-Smith J., Edwards C. R., Rees L. H., Dawson A. M. Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease. Gut. 1981 Nov;22(11):933–938. doi: 10.1136/gut.22.11.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fong Y., Moldawer L. L., Marano M., Wei H., Barber A., Manogue K., Tracey K. J., Kuo G., Fischman D. A., Cerami A. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Physiol. 1989 Mar;256(3 Pt 2):R659–R665. doi: 10.1152/ajpregu.1989.256.3.R659. [DOI] [PubMed] [Google Scholar]
  16. Giaffer M. H., North G., Holdsworth C. D. Controlled trial of polymeric versus elemental diet in treatment of active Crohn's disease. Lancet. 1990 Apr 7;335(8693):816–819. doi: 10.1016/0140-6736(90)90936-y. [DOI] [PubMed] [Google Scholar]
  17. Gotlin R. W., Dubois R. S. Nyctohemeral growth hormone levels in children with growth retardation and inflammatory bowel disease. Gut. 1973 Mar;14(3):191–195. doi: 10.1136/gut.14.3.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Green J. R., O'Donoghue D. P., Edwards C. R., Dawson A. M. A case of apparent hypopituitarism complicating chronic inflammatory bowel disease in childhood and adolescence. Acta Paediatr Scand. 1977 Sep;66(5):643–647. doi: 10.1111/j.1651-2227.1977.tb07962.x. [DOI] [PubMed] [Google Scholar]
  19. Grill B. B., Lange R., Markowitz R., Hillemeier A. C., McCallum R. W., Gryboski J. D. Delayed gastric emptying in children with Crohn's disease. J Clin Gastroenterol. 1985 Jun;7(3):216–226. doi: 10.1097/00004836-198506000-00007. [DOI] [PubMed] [Google Scholar]
  20. Kanof M. E., Lake A. M., Bayless T. M. Decreased height velocity in children and adolescents before the diagnosis of Crohn's disease. Gastroenterology. 1988 Dec;95(6):1523–1527. doi: 10.1016/s0016-5085(88)80072-6. [DOI] [PubMed] [Google Scholar]
  21. Kelts D. G., Grand R. J., Shen G., Watkins J. B., Werlin S. L., Boehme C. Nutritional basis of growth failure in children and adolescents with Crohn's disease. Gastroenterology. 1979 Apr;76(4):720–727. [PubMed] [Google Scholar]
  22. Kirschner B. S., Klich J. R., Kalman S. S., deFavaro M. V., Rosenberg I. H. Reversal of growth retardation in Crohn's disease with therapy emphasizing oral nutritional restitution. Gastroenterology. 1981 Jan;80(1):10–15. [PubMed] [Google Scholar]
  23. Kirschner B. S., Sutton M. M. Somatomedin-C levels in growth-impaired children and adolescents with chronic inflammatory bowel disease. Gastroenterology. 1986 Oct;91(4):830–836. doi: 10.1016/0016-5085(86)90683-9. [DOI] [PubMed] [Google Scholar]
  24. Layden T., Rosenberg F., Nemchausky G., Elson C., Rosenberg I. Reversal of growth arrest in adolescents with Crohn's disease after parenteral alimentation. Gastroenterology. 1976 Jun;70(6):1017–1021. [PubMed] [Google Scholar]
  25. Lee M. D., Zentella A., Vine W., Pekala P. H., Cerami A. Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6. Proc Natl Acad Sci U S A. 1987 May;84(9):2590–2594. doi: 10.1073/pnas.84.9.2590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. MacDonald T. T., Hutchings P., Choy M. Y., Murch S., Cooke A. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol. 1990 Aug;81(2):301–305. doi: 10.1111/j.1365-2249.1990.tb03334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mahida Y. R., Patel S., Wu K., Jewell D. P. Interleukin 2 receptor expression by macrophages in inflammatory bowel disease. Clin Exp Immunol. 1988 Dec;74(3):382–386. [PMC free article] [PubMed] [Google Scholar]
  28. Maury C. P., Teppo A. M. Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arthritis Rheum. 1989 Feb;32(2):146–150. doi: 10.1002/anr.1780320206. [DOI] [PubMed] [Google Scholar]
  29. McCaffery T. D., Nasr K., Lawrence A. M., Kirsner J. B. Severe growth retardation in children with inflammatory bowel disease. Pediatrics. 1970 Mar;45(3):386–393. [PubMed] [Google Scholar]
  30. McLain B. I., Davidson P. M., Stokes K. B., Beasley S. W. Growth after gut resection for Crohn's disease. Arch Dis Child. 1990 Jul;65(7):760–762. doi: 10.1136/adc.65.7.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Michie H. R., Manogue K. R., Spriggs D. R., Revhaug A., O'Dwyer S., Dinarello C. A., Cerami A., Wolff S. M., Wilmore D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. doi: 10.1056/NEJM198806093182301. [DOI] [PubMed] [Google Scholar]
  32. Michie H. R., Sherman M. L., Spriggs D. R., Rounds J., Christie M., Wilmore D. W. Chronic TNF infusion causes anorexia but not accelerated nitrogen loss. Ann Surg. 1989 Jan;209(1):19–24. doi: 10.1097/00000658-198901000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Milenkovic L., Rettori V., Snyder G. D., Beutler B., McCann S. M. Cachectin alters anterior pituitary hormone release by a direct action in vitro. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2418–2422. doi: 10.1073/pnas.86.7.2418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nadal D., Leppert D., Frei K., Gallo P., Lamche H., Fontana A. Tumour necrosis factor-alpha in infectious meningitis. Arch Dis Child. 1989 Sep;64(9):1274–1279. doi: 10.1136/adc.64.9.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oliff A., Defeo-Jones D., Boyer M., Martinez D., Kiefer D., Vuocolo G., Wolfe A., Socher S. H. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell. 1987 Aug 14;50(4):555–563. doi: 10.1016/0092-8674(87)90028-6. [DOI] [PubMed] [Google Scholar]
  36. Pimstone B. L., Barbezat G., Hansen J. D., Murray P. Studies on growth hormone secretion in protein-calorie malnutrition. Am J Clin Nutr. 1968 May;21(5):482–487. doi: 10.1093/ajcn/21.5.482. [DOI] [PubMed] [Google Scholar]
  37. Satsangi J., Wolstencroft R. A., Cason J., Ainley C. C., Dumonde D. C., Thompson R. P. Interleukin 1 in Crohn's disease. Clin Exp Immunol. 1987 Mar;67(3):594–605. [PMC free article] [PubMed] [Google Scholar]
  38. Seidman E. G. Nutritional management of inflammatory bowel disease. Gastroenterol Clin North Am. 1989 Mar;18(1):129–155. [PubMed] [Google Scholar]
  39. Selby W. S., Poulter L. W., Hobbs S., Jewell D. P., Janossy G. Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis. J Clin Pathol. 1983 Apr;36(4):379–384. doi: 10.1136/jcp.36.4.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sun X. M., Hsueh W. Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J Clin Invest. 1988 May;81(5):1328–1331. doi: 10.1172/JCI113459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Torti F. M., Dieckmann B., Beutler B., Cerami A., Ringold G. M. A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science. 1985 Aug 30;229(4716):867–869. doi: 10.1126/science.3839597. [DOI] [PubMed] [Google Scholar]
  42. Tracey K. J., Lowry S. F., Cerami A. Cachectin: a hormone that triggers acute shock and chronic cachexia. J Infect Dis. 1988 Mar;157(3):413–420. doi: 10.1093/infdis/157.3.413. [DOI] [PubMed] [Google Scholar]
  43. Tracey K. J., Vlassara H., Cerami A. Cachectin/tumour necrosis factor. Lancet. 1989 May 20;1(8647):1122–1126. doi: 10.1016/s0140-6736(89)92394-5. [DOI] [PubMed] [Google Scholar]
  44. Tracey K. J., Wei H., Manogue K. R., Fong Y., Hesse D. G., Nguyen H. T., Kuo G. C., Beutler B., Cotran R. S., Cerami A. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med. 1988 Mar 1;167(3):1211–1227. doi: 10.1084/jem.167.3.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Waage A., Halstensen A., Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. doi: 10.1016/s0140-6736(87)91728-4. [DOI] [PubMed] [Google Scholar]
  46. Wakefield A. J., Sawyerr A. M., Dhillon A. P., Pittilo R. M., Rowles P. M., Lewis A. A., Pounder R. E. Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction. Lancet. 1989 Nov 4;2(8671):1057–1062. doi: 10.1016/s0140-6736(89)91078-7. [DOI] [PubMed] [Google Scholar]
  47. Walton P. E., Cronin M. J. Tumor necrosis factor-alpha inhibits growth hormone secretion from cultured anterior pituitary cells. Endocrinology. 1989 Aug;125(2):925–929. doi: 10.1210/endo-125-2-925. [DOI] [PubMed] [Google Scholar]
  48. Ziegler E. J. Tumor necrosis factor in humans. N Engl J Med. 1988 Jun 9;318(23):1533–1535. doi: 10.1056/NEJM198806093182309. [DOI] [PubMed] [Google Scholar]

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