학술논문

Comparative effects of two type I interferons, human IFN-α and ovine IFN-τ on indoleamine-2,3-dioxygenase in primary cultures of human macrophages.
Document Type
Article
Source
Fundamental & Clinical Pharmacology. Feb2007, Vol. 21 Issue 1, p29-34. 6p. 1 Graph.
Subject
*INTERFERONS
*VIRUS diseases
*MENTAL depression
*DRUG side effects
*MACROPHAGES
Language
ISSN
0767-3981
Abstract
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- τ) has a more potent antiretroviral effect and is less toxic than human type I IFN- α. Effects of IFN- τ and IFN- α on IDO expression and activity in primary cultures of human macrophages were compared in parallel to those of IFN- γ, considered as one of the most potent IDO inducer. We found that both IFN- α and IFN- τ were poor inducers of IDO compared with IFN- γ. However, IDO activation was slightly and significantly lower with ovine IFN- τ than human IFN- α, suggesting that ovine IFN- τ might have a lower impact on serotoninergic pathway compared with human IFN- α. [ABSTRACT FROM AUTHOR]