title: Glutamine-enriched enteral nutrition increases in vitro interferon-gamma production but does not influence the in vivo specific antibody response to KLH after severe trauma. A prospective, double blind, randomized clinical study.
abstract: OBJECTIVE
  Severe trauma leads to an immune suppression, characterized by a Type 2 T-lymphocyte response, contributing to the susceptibility of infectious complications. Plasma concentrations of glutamine (GLN), the preferred fuel for immunocompetent cells, severely decrease after trauma. Since administering glutamine-enriched enteral nutrition (EN) reduces infectious complications in trauma patients, we compared the effect of glutamine-enriched EN with an isocaloric, isonitrogenous enteral control (Con) feeding, on the Type 1 and 2 T-lymphocyte responses.
  
  
  METHODS
  Thirty-eight trauma patients (Injury Severity Score >20) were sensitized with Keyhole Limpet Hemocyanin (KLH) within 12 h after trauma (17 GLN group). Healthy volunteers served as controls (HV, n=17). In vitro interferon-gamma (IFN-gamma), IL-4 and IL-10 productions of phytohemagglutinin (PHA)-stimulated PBMCs were determined by ELISA technique. KLH-specific IgG, IgM, IgA, IgG1, IgG2, IgG3, IgG4 and IgE were measured in serum.
  
  
  RESULTS
  Both patient groups had a low in vitro (IFN-) production of stimulated PBMCs on d1. On d14, the IFN-gamma production increased significantly in the glutamine group as compared to the controls. IL-4 production was not different between the groups on day 1 (d1). On d14, IL-4 decreased in the control group as compared to the glutamine group. KLH-specific antibodies reached comparable levels in both patients groups and healthy volunteers at d14.
  
  
  CONCLUSIONS
  In conclusion, trauma caused a suppressed in vitro cellular immune response presented by a low IFN-gamma production and depressed the IgG and IgM response to KLH directly after trauma. Glutamine increased IFN-gamma production (d14), maintained a normal IL-4 production, but was not acquired for the development of KLH-specific humoral response on d14, in sync suggesting that dietary glutamine supports the restoration of the Type-1 T-lymphocyte responsiveness.
authors.affiliation: Department of Surgery, VU University Medical Center, PO. Box 7057, Amsterdam 1007 MB, The Netherlands.
authors.forename: Petra G
authors.initials: PG
authors.lastname: Boelens
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Houdijk
authors.forename: Johanna C M
authors.initials: JC
authors.lastname: Fonk
authors.forename: Juan C
authors.initials: JC
authors.lastname: Puyana
authors.forename: Henk J Th M
authors.initials: HJ
authors.lastname: Haarman
authors.forename: Mary E
authors.initials: ME
authors.lastname: von Blomberg-van der Flier
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000906:Antibodies / Q000097:blood; D004311:Double-Blind Method; D004750:Enteral Nutrition; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D009104:Multiple Trauma / Q000276:immunology*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005973:Glutamine; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin