{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:24:05Z","timestamp":1781105045255,"version":"3.54.1"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,9,13]]},"abstract":"<jats:p>\n                    Inflammatory diseases frequently impair linear growth. Crohn's disease inhibits growth in up to one third of affected children. In rats with trinitrobenzenesulphonic acid-induced colitis, 40% of growth impairment is attributable to inflammation, with the rest being due to undernutrition. In transgenic mice without inflammation, raised IL-6 retards growth, suppressing insulin-like growth factor (IGF)-I. We hypothesized that IL-6, induced by intestinal inflammation, suppresses growth and inhibits IGF-I expression. Therefore, an anti-IL-6 Ab was given to rats with trinitrobenzene-sulphonic acid colitis. The Ab did not improve nutrient intake or decrease inflammation compared with untreated disease controls, but it significantly restored linear growth (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.023) and increased IGF-I (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.05). In humans, the IL-6 -174 G\/C promoter polymorphism affects IL-6 transcription, with the GG genotype inducing the greatest IL-6 levels. Because IL-6 is increased in Crohn's disease, we further hypothesized that growth failure would vary with the IL-6 -174 genotype. At diagnosis, among 153 children with Crohn's disease, those with the IL-6 GG genotype were more growth-retarded than those with the GC or CC genotypes (height SD score, -0.51 vs. -0.10;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.031). Also, the patients with the IL-6 GG genotype had higher circulating levels of C-reactive protein, an IL-6-induced product (36 vs. 18 mg\/dl,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.028). However, their risk of developing Crohn's disease was similar to other genotypes when compared with 351 healthy controls (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.7). Thus, the IL-6 -174 genotype mediates growth failure in children with Crohn's disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0503589102","type":"journal-article","created":{"date-parts":[[2005,9,6]],"date-time":"2005-09-06T20:33:41Z","timestamp":1126038821000},"page":"13260-13265","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the \u2013174 IL-6 G\/C polymorphism in children"],"prefix":"10.1073","volume":"102","author":[{"given":"Andrew","family":"Sawczenko","sequence":"first","affiliation":[{"name":"Research Centre for Gastroenterology, Institute of Cell and Molecular Science, and Department of Pediatric Endocrinology, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 2AD, United Kingdom; and Paediatric Gastroenterology and Nutrition, Department of Women and Child Health, Astrid Lindgren Children's Hospital, Karolinska Institute, S-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omeia","family":"Azooz","sequence":"additional","affiliation":[{"name":"Research Centre for Gastroenterology, Institute of Cell and Molecular Science, and Department of Pediatric Endocrinology, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 2AD, United Kingdom; and Paediatric Gastroenterology and Nutrition, Department of Women and Child Health, Astrid Lindgren Children's Hospital, Karolinska Institute, S-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Paraszczuk","sequence":"additional","affiliation":[{"name":"Research Centre for Gastroenterology, Institute of Cell and Molecular Science, and Department of Pediatric Endocrinology, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 2AD, United Kingdom; and Paediatric Gastroenterology and Nutrition, Department of Women and Child Health, Astrid Lindgren Children's Hospital, Karolinska Institute, S-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Idestrom","sequence":"additional","affiliation":[{"name":"Research Centre for Gastroenterology, Institute of Cell and Molecular Science, and Department of Pediatric Endocrinology, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 2AD, United Kingdom; 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