title: Fundamental mechanisms of growth failure in inflammatory bowel disease.
abstract: Growth failure is common in children with inflammatory bowel disease (IBD) and has been attributed chiefly to undernutrition. Liquid enteral feeding can reverse the calorie deficit and increase growth velocity. The inflammatory process per se may also directly inhibit linear growth. After institution of enteral nutrition, significant changes in serum growth factors and inflammatory indices have been observed before any changes in nutritional parameters [Bannerjee et al., Gastroenterology 2000;118:A526]. In rats with trinitrobenzenesulphonic acid (TNBS)-induced colitis, about 60% of the final growth impairment can be attributed to undernutrition, inflammation accounting for the remaining growth deficit. Young patients with Crohn's disease and growth failure have normal stimulated and spontaneous growth hormone (GH) secretion and reduced plasma concentrations of insulin-like growth factor-1 (IGF-I), suggesting a degree of GH resistance. Rats with TNBS colitis also have normal plasma GH and reduced IGF-I concentrations, mediated by a combination of undernutrition and active inflammation. Immunoneutralization of interleukin-6 (IL-6) increases hepatic IGF-I mRNA expression, plasma concentrations of IGF-I and linear growth. In contrast, administration of anti-tumour necrosis factor-alpha antibodies (TNF-ab) had no effect on IGF-I in this model. TNFab did, however, increase linear growth, suggesting inhibitory effects of TNF-alpha on the growth axis by mechanisms other than reduction in IGF-I. Preliminary data suggests that TNF-alpha inhibits maturation of growth plate chondrocytes. We have identified IL-6 receptors on growth plate chondrocytes but to date have not identified the effect, if any, of IL-6 directly at the growth plate.
authors.affiliation: Department of Adult and Paediatric Gastroenterology, Barts and the London, Queen Mary School of Medicine and Dentistry, London, UK. a.b.ballinger@mds.qmw.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Ballinger
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000150:complications / Q000503:physiopathology; D003424:Crohn Disease / Q000150:complications / Q000503:physiopathology; D016207:Cytokines; D006130:Growth Disorders / Q000209:etiology*; D006728:Hormones; D006801:Humans; D018836:Inflammation Mediators; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000503:physiopathology; D009747:Nutritional Physiological Phenomena
chemical_list: D016207:Cytokines; D006728:Hormones; D018836:Inflammation Mediators