Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

Ambra Hernis,Marco Rovaris,Roberta Mancuso,Simone Agostini,Dietmar Fuchs,Domenico Caputo,Mario Clerici

doi:10.1371/journal.pone.0130715

Abstract

BackgroundInterferon 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.MethodsIDO 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).ResultsIDO 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.ConclusionsMeasurement 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.

Highlights

Multiple Sclerosis (MS) is a chronic demyelinating neurodegenerative disorder of the central nervous system (CNS)
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
Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of Relapsing remitting MS (RR-MS)

Summary

Introduction

Multiple Sclerosis (MS) is a chronic demyelinating neurodegenerative disorder of the central nervous system (CNS) This disease is characterized by perivascular inflammatory lesions in the white matter of the CNS, demyelination, and axonal damages and is probably initiated by autoreactive T lymphocytes directed toward CNS antigens. Indoleamine 2,3 dioxygenase (IDO) is an enzyme that catalyses the first and rate-limiting step in the kynurenine (Kyn) pathway, i.e. the degradation of the essential amino acid tryptophan (Trp) into Kyn in extrahepatic tissues. This pathway plays a role in the pathogenesis of neuroinflammatory and neurodegenerative disorders. 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

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