title: Growth hormone reduces the severity of fibrosis associated with chronic intestinal inflammation.
abstract: OBJECTIVE
  Growth hormone (GH) is used to treat growth delay in children with Crohn's disease and in patients with short-bowel syndrome. GH can increase collagen accumulation in intestinal mesenchymal cells, raising concern that GH therapy could exacerbate fibrosis in patients with Crohn's disease. We tested if GH treatment altered inflammation or fibrosis during chronic, experimental granulomatous enterocolitis.
  
  
  METHODS
  Ileum and cecum of Lewis rats were subserosally injected with peptidoglycan-polysaccharide (PG-APS) or control human serum albumin. At the onset of chronic PG-APS-induced inflammation, rats were administered recombinant human GH or vehicle for 14 days. Fibrosis and inflammation were quantified by gross gut disease scoring, histologic scoring, type I collagen, and cytokine expression in cecum. Abundance and localization of suppressor of cytokine signaling-3 (SOCS-3) messenger RNA and/or protein were determined in cecum. Effect of GH, cytokines, or PG-APS on SOCS-3 synthesis was measured in intestinal myofibroblasts. Myofibroblasts overexpressing SOCS-3 were used to test whether SOCS-3 inhibits collagen accumulation.
  
  
  RESULTS
  In PG-APS-injected rats, GH modestly reduced gross adhesions and mesenteric contractions, cecal fibrosis score, and collagen expression, but had no effect on intestinal inflammation. GH increased SOCS-3 messenger RNA and protein abundance in PG-APS rats and SOCS-3 messenger RNA was localized to the periphery of granulomas. GH in combination with cytokines or PG-APS, but not alone, induced SOCS-3 synthesis in intestinal myofibroblasts. Myofibroblasts overexpressing SOCS-3 showed reduced cytokine-induced collagen accumulation.
  
  
  CONCLUSIONS
  GH modestly reduces intestinal fibrosis associated with chronic experimental enterocolitis and stimulates expression of antifibrogenic SOCS-3, suggesting that GH therapy in inflammatory bowel disease should not exacerbate fibrosis.
authors: Department of Cell and Molecular Pathology, The Univesity of North Carolina at Chapel Hill, 27599-7545, USA.
authors: Arianne L
authors: AL
authors: Theiss
authors: C Randall
authors: CR
authors: Fuller
authors: James G
authors: JG
authors: Simmons
authors: Bo
authors: B
authors: Liu
authors: R Balfour
authors: RB
authors: Sartor
authors: P Kay
authors: PK
authors: Lund
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013006:Growth Hormone / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007596:Joints / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D013047:Specific Pathogen-Free Organisms; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D011134:Polysaccharides; D012333:RNA, Messenger; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen