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

Background Interferon gamma (IFN-gamma) 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 inmultiple sclerosis (MS) patients. Methods IDO and interferon-gamma (IFN-gamma) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration - a protein released by macrophages upon IFN-gamma 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-gamma 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-gamma 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.