Abstract
Tryptophan is a constituent of proteins and in parallel it represents a source for mainly two pivotal biochemical pathways the generation of 5-hydroxytryptamine (serotonin), and the formation of kynurenine by the enzymes tryptophan pyrrolase (TP) and indoleamine 2,3-dioxygenase (IDO). IDO is induced by interferon-g (IFN-g ) in a broad variety of cells. Therefore, enhanced tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e.g. infectious diseases, autoimmune diseases, malignant diseases as well as in pregnancy. IFN-g -derived tryptophan degradation may represent an effector mechanism within in the comprehensive network of immune stimulation. In addition, the cytostatic and, respectively, antiproliferative properties on e.g., T-lymphocytes may contribute to the immunomodulatory function of IFN-g . However, especially in states of persistent immune activation increased tryptophan catabolism leads to the depletion of free serum tryptophan and to the accumulation of neuroactive kynurenine metabolites. As a consequence, serotonergic functions may be affected, and the neurotoxic properties of kynurenine derivatives may lead to neuronal disorders evoking neurological/psychiatric symptoms. This notion provides a basis for the better understanding of mood disorders and related syptoms in chronic diseases. Moreover, IDO could represent a link between the immunological network and neuroendocrine functions with far reaching consequences regarding to the psychological status of patients.
Keywords: hydroxytryptamine, tryptophane pyrrolase, interferon, immunosuppressive, kynurenine derivatives, major depression, immune activatio
Current Drug Metabolism
Title: Interferon gama induced Tryptophan Degradation Neuropsychiatric and Immunological Consequences
Volume: 1 Issue: 2
Author(s): B. Widner, M. Ledochowski and D. Fuchs
Affiliation:
Keywords: hydroxytryptamine, tryptophane pyrrolase, interferon, immunosuppressive, kynurenine derivatives, major depression, immune activatio
Abstract: Tryptophan is a constituent of proteins and in parallel it represents a source for mainly two pivotal biochemical pathways the generation of 5-hydroxytryptamine (serotonin), and the formation of kynurenine by the enzymes tryptophan pyrrolase (TP) and indoleamine 2,3-dioxygenase (IDO). IDO is induced by interferon-g (IFN-g ) in a broad variety of cells. Therefore, enhanced tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e.g. infectious diseases, autoimmune diseases, malignant diseases as well as in pregnancy. IFN-g -derived tryptophan degradation may represent an effector mechanism within in the comprehensive network of immune stimulation. In addition, the cytostatic and, respectively, antiproliferative properties on e.g., T-lymphocytes may contribute to the immunomodulatory function of IFN-g . However, especially in states of persistent immune activation increased tryptophan catabolism leads to the depletion of free serum tryptophan and to the accumulation of neuroactive kynurenine metabolites. As a consequence, serotonergic functions may be affected, and the neurotoxic properties of kynurenine derivatives may lead to neuronal disorders evoking neurological/psychiatric symptoms. This notion provides a basis for the better understanding of mood disorders and related syptoms in chronic diseases. Moreover, IDO could represent a link between the immunological network and neuroendocrine functions with far reaching consequences regarding to the psychological status of patients.
Export Options
About this article
Cite this article as:
Widner B., Ledochowski M. and Fuchs D., Interferon gama induced Tryptophan Degradation Neuropsychiatric and Immunological Consequences, Current Drug Metabolism 2000; 1 (2) . https://dx.doi.org/10.2174/1389200003339063
DOI https://dx.doi.org/10.2174/1389200003339063 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Metabolism-Mediated Xenobiotic Toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Mesenchymal Stem Cells Induced In Vitro Generated Regulatory-T Cells: Potential Soldiers of Transplantation Biology
Current Biotechnology Cosignaling Complexity Gets More Convoluted: The Emerging Importance of the B7-Like Butyrophilin Family of Immune Regulators
Current Immunology Reviews (Discontinued) Vitamin D Receptor as a Drug Discovery Target
Mini-Reviews in Medicinal Chemistry New Therapies in SLE
Recent Patents on Inflammation & Allergy Drug Discovery Gene Therapy for Immunologic Tolerance: Using Bone Marrow-Derived Cells to Treat Autoimmunity and Hemophilia
Current Stem Cell Research & Therapy Some Important Dietary Polyphenolic Compounds: An Anti-inflammatory and Immunoregulatory Perspective
Mini-Reviews in Medicinal Chemistry Triggering of Apoptosis and Pro-Inflammatory Cytokines in NK Cells: Regulation by Cyclosporin A
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Regulatory T Cell Therapy for Type I Diabetes Targeting on β Cell Associated Autoantigens
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation
Current Drug Delivery Micro- and Nano-particulate Strategies for Antigen Specific Immune Tolerance to Treat Autoimmune Diseases
Pharmaceutical Nanotechnology Therapeutic Monoclonal Antibodies and Multiple Sclerosis: The Essentials
Medicinal Chemistry Cough in Respiratory and Autoimmune Disorders
Current Respiratory Medicine Reviews The Study of HLA Class II and Autoimmune Diabetes
Current Molecular Medicine Targeting Regulatory T Cells in the Treatment of Type 1 Diabetes Mellitus
Current Molecular Medicine The Impact of Post-Genomics Approaches in Neurodegenerative Demyelinating Diseases: The Case of Guillain-Barré Syndrome
Current Medicinal Chemistry Catecholamines: Physiological Immunomodulators During Health and Illness
Current Medicinal Chemistry Autoimmunity-Inducing Metals (Hg, Au and Ag) Modulate Mast Cell Signaling, Function and Survival
Current Pharmaceutical Design Autoantibody-Induced Formation of Immune Complexes in Normal Human Serum
Current Pharmaceutical Design Current and Future Therapies Targeting the Immune System in Multiple Sclerosis
Current Pharmaceutical Biotechnology The Role of HLA Promoters in Autoimmunity
Current Pharmaceutical Design