title: Exploring and Enhancing the Anti-Inflammatory Properties of Polymeric Formula.
abstract: Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti-inflammatory properties of EEN.
  
  
  
  Glutamine, arginine, vitamin D3, and α linolenic acid (ALA), present in PF, along with curcumin, were identified as immunoactive nutrient therapies. Tumor necrosis factor (TNF)-α-exposed HT-29 colonic epithelial cells were used to investigate the immunosuppressive activity of the nutrients by assessing their effect on cell viability, cell activity, chemokine response (interleukin-8 [IL-8]), nuclear factor (NF)-κB, P38 mitogen-activated protein kinase, IκB kinase (Iκκ), and nitric oxide (NO).
  
  
  
  Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D3, but not ALA, significantly attenuated IL-8 production. Glutamine and arginine led to phosphorylation blockade of the signaling components in NF-κB and P38 pathways, reduction in kinase activity, and enhancement in NO production. Combining glutamine, arginine, and curcumin at optimal concentrations completely abolished the IL-8 response.
  
  
  
  These data indicate that glutamine, arginine, and vitamin D3can suppress inflammation at concentrations equivalent to those used in PF. The mechanisms of this action were mediated through influencing the NF-κB and P38 cascades. Glutamine and arginine-fortified PF with curcumin might be a promising option to enhance the effectiveness and expand the scope of EEN therapy in CD treatment.
authors.affiliation: 1 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Moftah H
authors.initials: MH
authors.lastname: Alhagamhmad
authors.affiliation: 1 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.|2 Paediatrics, University of Otago, Christchurch, New Zealand.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Day
authors.affiliation: 1 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.|3 Department of Gastroenterology, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lemberg
authors.affiliation: 1 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Leach
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000032:analysis; D003424:Crohn Disease / Q000628:therapy; D004750:Enteral Nutrition; D005973:Glutamine / Q000032:analysis; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000628:therapy; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019999:Pharmaceutical Solutions / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D016328:NF-kappa B; D019999:Pharmaceutical Solutions; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D005973:Glutamine; D002762:Cholecalciferol; D009569:Nitric Oxide; D001120:Arginine; D048051:p38 Mitogen-Activated Protein Kinases
keywords: amino acids; curcumin; intestinal inflammation; polymeric formula; signaling pathways