title: Serum Immune System Biomarkers Neopterin and Interleukin-10 Are Strongly Related to Tryptophan Metabolism in Healthy Young Adults.
abstract: Changes in tryptophan metabolism through the vitamin B-6-dependent kynurenine pathway have been linked to activation of the immune system.
  
  
  
  We hypothesized that blood concentrations of tryptophan and its catabolites were associated with biomarkers relevant to inflammatory processes in healthy noninflamed subjects.
  
  
  
  Healthy young adults (n = 737) aged 18-28 y without any known diseases or clinical evidence of inflammation provided blood samples for analysis of serum tryptophan/kynurenine metabolites, neopterin, C-reactive protein (CRP), and plasma pyridoxal 5'-phosphate (PLP) with LC-tandem mass spectrometry methodologies. A panel of cytokines was measured in serum by using high-sensitivity ELISA assays. Anthropometric and lifestyle data were collected by questionnaire. Multiple linear regression analysis to determine the effect of measured serum cytokine concentrations as predictors of tryptophan metabolites was performed on inverse normal-rank transformations of the data, adjusted for sex, body mass index, smoking, alcohol intake, and contraceptive use in women.
  
  
  
  Median serum CRP and neopterin concentrations were well below established clinical cutoffs for inflammation. We observed significant positive associations between serum interleukin-10 (IL-10) and serum kynurenine (P = 0.0002), the kynurenine-to-tryptophan ratio (KTR) (P = 0.003), 3-hydroxykynurenine (P = 0.01), and 3-hydroxyanthranilic acid (P = 0.04). Serum neopterin was positively associated with kynurenine, the KTR (both P < 0.0001), and anthranilic acid (P = 0.004), and was negatively associated with serum tryptophan (P = 0.01) and PLP (P < 0.0001). Serum tumor necrosis factor α was also negatively associated with tryptophan (P < 0.001).
  
  
  
  In healthy young adults with no apparent inflammatory conditions, serum tryptophan metabolites are significantly associated with key immune system biomarkers. The observed association between IL-10 and kynurenine is unexpected and suggests that kynurenine-linked mechanisms promoting negative regulation of inflammatory responses are associated with normal immune homeostasis.
authors.affiliation: School of Medicine and.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Deac
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.affiliation: School of Biochemistry and Immunology, Trinity College Dublin, Ireland;
authors.forename: Clair M
authors.initials: CM
authors.lastname: Gardiner
authors.affiliation: Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA;
authors.forename: Barry
authors.initials: B
authors.lastname: Shane
authors.affiliation: School of Biochemistry and Immunology, Trinity College Dublin, Ireland;
authors.forename: Louise
authors.initials: L
authors.lastname: Quinn
authors.affiliation: Bevital AS, Bergen, Norway; and.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Bevital AS, Bergen, Norway; and.
authors.forename: Adrian
authors.initials: A
authors.lastname: McCann
authors.affiliation: Bevital AS, Bergen, Norway; and.
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.affiliation: Section of Pharmacology, Institute of Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD;
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.affiliation: School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Ireland; amolloy@tcd.ie.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood; D016014:Linear Models; D008297:Male; D019798:Neopterin / Q000097:blood*; D011732:Pyridoxal Phosphate / Q000097:blood; D011795:Surveys and Questionnaires; D014364:Tryptophan / Q000097:blood* / Q000378:metabolism; D025101:Vitamin B 6 / Q000097:blood; D055815:Young Adult; D062367:ortho-Aminobenzoates / Q000097:blood
chemical_list: D015415:Biomarkers; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D016753:Interleukin-10; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D011732:Pyridoxal Phosphate; D019798:Neopterin; D025101:Vitamin B 6; D014364:Tryptophan; D002097:C-Reactive Protein
keywords: cytokines; interleukin-10; kynurenine; neopterin; tryptophan