Increased indoleamine 2,3-dioxygenase (IDO) activity in idiopathic generalized epilepsy

Abstract

Indoleamine 2,3-dioxygenase (IDO) is a cytokine-inducible enzyme that participates in tryptophan (trp) and serotonin metabolism with an ability to modulate neuroinflammation. Several recent studies have shown associations between cytokines and epilepsy. In this study we investigated whether activation of IDO is associated with epilepsy. Kynurenine (kyn)/trp serum ratio, as an indicator of IDO activity was analyzed in 271 carefully classified epilepsy patients, and 309 healthy adults. IDO activity was increased in patients with unclassified idiopathic generalized epilepsy (IGE) (n=11; p=0.05), in juvenile myoclonic epilepsy (JME) (n=25; p=0.04) and in patients those with temporal lobe epilepsy but no hippocampal sclerosis (TLE-HS) (n=103; p=0.05) compared to the control subjects. In patients with idiopathic (but not cryptogenic or symptomatic) etiology of epilepsy, IDO activity was increased compared to the control subjects (p<0.05). Patients with extra-TLE or TLE+HS had IDO activity comparable to the control subjects. Patients who were one-month seizure-free prior to sampling had increased IDO activity compared to the control subjects (p=0.03). Increased IDO activity appeared to be associated with idiopathic generalized epilepsies such as unclassified IGE and JME, two of the most common types of primary generalized epilepsy. We also found a trend of increased IDO activity in patients with TLE-HS. Our results suggest that increased IDO activity may represent an adaptive metabolic phenomenon in epilepsy, which may also have a neuroprotective or anticonvulsive role by downregulating neuroinflammation in the brain.