Current Drug Metabolism - Volume 8, Issue 3, 2007

Almost 30 years ago, indoleamine 2,3-dioxygenase (IDO) was discovered as a tryptophan-degrading enzyme, which is inducible by interferons. IDO converts tryptophan to N-formyl-kynurenine, and this catabolism of the essential amino acid turned out as an important antiproliferative activity, which is directed to halt reproduction of pathogens in infected cells and to stop malignant growth. Consequently, induction of IDO was c Read More

Tryptophan oxidation occurs via both extra-hepatic and hepatic pathways. Although these pathways share many enzymes, the first and rate-limiting step in each pathway is carried out by two different enzymes: Indoleamine-Pyrrole 2,3 Dioxygenase (INDO) and Tryptophan 2,3-Dioxygenase (TDO2). Over the course of the last forty years extensive and detailed research by many groups have led to an understanding of some o Read More

Much attention has been paid in initial biochemical studies on the ability of indoleamine 2,3-dioxygenase to use superoxide as substrate to cleave tryptophan to N-formyl kynurenine. This ability, however, is limited to the ferric form of the enzyme only, whereas the ferrous form requires oxygen rather than superoxide as substrate. As long as the enzyme is held in the ferrous form, high yield formation of product proceeds from th Read More

The mechanism of maternal immunotolerance of the semiallogeneic fetus has been a matter of intense investigation. The tryptophan- degrading enzyme indoleamine 2,3-dioxygenase (IDO) is reported to be critically implicated. This article discusses findings pertaining to the role of IDO in pregnancy, its location at the feto-maternal interface, systemic induction of IDO in pregnancy and the association of IDO to spontaneous Read More

Plasmacytoid dendritic cells (pDCs) represent a specialized cell population that produces large amounts of type I interferons, the so-called natural interferon-producing cells. Recently, murine and human pDCs have been credited with a unique ability to express indoleamine 2,3-dioxygenase (IDO) and to mediate immunosuppression in specific settings. This suggests an important role for IDOexpressing pDCs in controlling the Read More

Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressive activity, which could contribute to the immune dysfunction observed in HIV-infected patients. In this r Read More

Human immunodeficiency virus type 1 (HIV) infection is characterized by progressive immunodeficiency despite of an overwhelming cellular immune activation. Patients show highly elevated serum/plasma concentrations of the proinflammatory cytokine interferon-γ (IFN-γ ), which induces human monocytes to form neopterin, to produce reactive oxygen species (ROS) and in parallel, to degrade tryptophan. Enhanc Read More

Tryptophan metabolism occurs via the protohemoprotein enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3- dioxygenase (IDO), the latter action of which has a number of effects in the body including both antimicrobial defence and immune regulation. Whilst the antimicrobial action of IDO is largely due to depletion of the essential amino acid tryptophan, the immune regulatory function of IDO is still unclear an Read More

Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1- methyl-tryptophan causes a sudden catas Read More

Hematopoietic stem cell transplantation (HSCT) is complicated by unwelcome side-effects that arise on the basis of an altered immune system. Infectious complications and alloreactive T-cell responses trigger a process of ongoing immune activation and inflammation. Negative-feedback mechanisms to counteract inflammation involve the induction of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO), whi Read More

The Th1-type cytokine interferon-γ (IFN-γ ) is known as one of the most versatile players of the immune system. In transplantation immunology IFN-γ has been shown to have contradictory effects on allograft survival via effects on both, the immune system and on the graft itself. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO), widely distributed in mammals, is induced preferentially by IFN-γ . IDO Read More

In the pathogenesis of depressive symptoms the neurotransmitter serotonin plays an important role - although the underlining mechanisms are still not clear. The synthesis of serotonin is dependent on the availability of tryptophan - an amino acid that is linked to the immune system by its catabolism via the enzyme indoleamine-2,3-dioxygenase (IDO). Based on this connection research approaches addressing different clini Read More

Morbid obesity is associated with low-grade systemic inflammation and immune activation. Thereby various proinflammatory cytokines like TNF-α , IL-1, IL-6, IFN-γ and hormones, such as leptin are synthesized and released in human adipose tissue. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is widely distributed in mammals and is inducible preferentially by IFN-γ . IDO degrades the essential amino acid t Read More