title: Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing-Remitting Multiple Sclerosis.
abstract: BACKGROUND
  Interferon gamma (IFN-γ) production induces the transcription of indoleamine 2,3 dioxygenase (IDO) resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS) patients.
  
  
  METHODS
  IDO and interferon-γ (IFN-γ) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR)-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS) and 15 healthy controls (HC). PBMCs samples in AMS patients were collected before (BT-AMS) and during glucocorticoids-based therapy (DT-AMS).
  
  
  RESULTS
  IDO expression was increased and IFN-γ was decreased (p<0.001) in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001). Serum neopterin concentration followed the same trend as IDO expression and activity.
  
  
  CONCLUSIONS
  Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS.
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Hernis
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Agostini
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80-82, A-6020, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Don C. Gnocchi Foundation ONLUS, Piazza Morandi 3, 20100, Milan, Italy; Department of Physiopathology and Transplantation, University of Milano, Via Fratelli Cervi 93, 20090, Segrate, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000201:enzymology*; D019798:Neopterin / Q000097:blood*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D019798:Neopterin; D007371:Interferon-gamma