Comparative effects of two type I interferons, human IFN-alpha and ovine IFN-tau on indoleamine-2,3-dioxygenase in primary cultures of human macrophages.
Type I interferons (IFNs) are widely used to treat viral diseases. Depressive symptoms and suicide attempts are common neuropsychiatric side-effects during treatment with type I IFNs. Activation of indoleamine-2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the kynurenine pathway by IFNs, leads to an increase in tryptophan (Trp) catabolism. Low levels of Trp lead to decrease of serotonin synthesis, which is likely to be related to the depressive symptoms. Ovine type I interferon-tau (IFN-tau) has a more potent antiretroviral effect and is less toxic than human type I IFN-alpha. Effects of IFN-tau and IFN-alpha on IDO expression and activity in primary cultures of human macrophages were compared in parallel to those of IFN-gamma, considered as one of the most potent IDO inducer. We found that both IFN-alpha and IFN-tau were poor inducers of IDO compared with IFN-gamma. However, IDO activation was slightly and significantly lower with ovine IFN-tau than human IFN-alpha, suggesting that ovine IFN-tau might have a lower impact on serotoninergic pathway compared with human IFN-alpha.