Manipulation of indoleamine 2,3 dioxygenase; a novel therapeutic target for treatment of diseases

Abstract

Background: The discovery of indoleamine 2,3-dioxygenase (IDO) as a modulator for the maintenance of fetomaternal immuno-privileged state has been heralded as a significant step in further defining the role of IDO in immunobiology. IDO is an IFN-inducible, intracellular enzyme that catalyzes the initial and rate-limiting step in the degradation of the essential amino acid, tryptophan. It has been suggested that IDO has the capacity to regulate the immune system via two discrete mechanisms; firstly the deprivation of tryptophan, which is essential for T cell proliferation and via the cytotoxic effects of tryptophan metabolites on T_H1 cell survival. Methods: The sources of information used to prepare the paper are published work on Pubmed/Medline. In this review, we examine the therapeutic role of modulating IDO activity a variety of disease states including tumour tolerance, chronic infection, transplant rejection, autoimmunity and asthma. We propose that IDO represents a novel therapeutic target for the treatment of these diseases. We also explore the diverse strategies which are being employed, either to augment or to inhibit IDO activity in order to modify various disease processes. The limitations associated with these strategies are also scrutinized.

Keywords::

• autoimmune diseases and asthma
• chronic infection
• IDO
• transplant rejection
• tumour tolerance

Acknowledgements

Because of space restrictions, the authors were able to cite only a fraction of the relevant literature and apologize to any colleagues whose contributions may not be appropriately acknowledged in this review.