Antiviral activity of interferon-γ involved in impaired immune function in infectious diseases

Abstract

Abstract Pro-inflammatory cytokines like interferon-γ (IFN-γ) play dominant roles in pathophysiologic conditions like infections, cardiovascular and neurodegenerative disorders and autoimmune syndromes. As part of its antimicrobial and immunomodulatory armature, the tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase (IDO) is mainly up-regulated in dendritic cells (DCs) and phagocytes by pro-inflammatory stimuli, most notably IFN-γ. By the breakdown of the essential amino acid l-tryptophan along the kynurenine pathway, IDO plays a key role in the inhibition of cell proliferation including that of activated T cells, thereby supporting immune tolerance in mammalian pregnancy, tumor development, allergic inflammation and allotransplantation. IFN-γ-induced tryptophan deprivation also seems to be involved in the pathogenesis of anemia and cachexia when erythroid progenitor cells suffer from insufficient amino acid supply or when protein biosynthesis of the organism is restricted by diminished tryptophan availability. This biochemical cascade seems also to be involved in the production of potentially neurotoxic tryptophan catabolites such as quinolinic acid, which ultimately leads to the development of neuropsychiatric symptoms like cognitive impairment and depression especially in patients suffering from severe and chronic infections.