scholarly journals Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 734
Author(s):  
Masaru Tanaka ◽  
Fanni Tóth ◽  
Helga Polyák ◽  
Ágnes Szabó ◽  
Yvette Mándi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Psychiatric Disorders ◽  
Inflammatory Cytokines ◽  
Metabolic Pathway ◽  
Autism Spectrum ◽  
Xanthurenic Acid ◽  
Low Grade ◽  
Post Traumatic Stress ◽  
Wide Range

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder.

scholarly journals Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

2021 ◽  
Author(s):  
Masaru Tanaka ◽  
Fanni Tóth ◽  
Helga Polyák ◽  
Ágnes Szabó ◽  
Yvette Mándi ◽  
...  
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Metabolic Pathway ◽  
Autism Spectrum ◽  
Xanthurenic Acid ◽  
Low Grade ◽  
Post Traumatic Stress ◽  
Indoleamine 2 ◽  
Aryl Hydrocarbon ◽  
Wide Range

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Psychoneuroimmunology of Post-Traumatic Stress Disorder

2018 ◽  
Author(s):  
Rebecca Hannah Bind ◽  
Carmine M. Pariante
Keyword(s):  
Immune System ◽  
Immune Function ◽  
Psychiatric Disorders ◽  
Post Traumatic Stress Disorder ◽  
Immune Activation ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Post Traumatic ◽  
Immune Changes

This chapter reviews the evidence linking post-traumatic stress disorder (PTSD) with changes in immune function. The chapter starts with a brief explanation of the components of the immune system, including cytokines, and of the mechanisms linking psychological and psychiatric phenomena with changes in immune function (i.e., psychoneuroimmunology). Specific studies on PTSD are then described, including the potential neurobiological and health consequences of these immune changes and, finally, the effects of PTSD treatment on both symptomology and the immune system. While there is a consistent pattern of findings indicating increased immune activation in this condition, there is a paucity of research on the immunological correlates of PTSD, especially compared with the large number of immunological studies on depression and other psychiatric disorders.

New activity of yamamarin, an insect pentapeptide, on immune system of mealworm,Tenebrio molitor

2017 ◽  
Vol 108 (3) ◽  
pp. 351-359 ◽  
Author(s):  
K. Walkowiak-Nowicka ◽  
G. Nowicki ◽  
M. Kuczer ◽  
G. Rosiński
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cellular Responses ◽  
Tenebrio Molitor ◽  
Immunotropic Activity ◽  
Silk Moth ◽  
Wide Range ◽  
Selected Functions ◽  
Active Substances ◽  
Stimulation Of

AbstractIn insects, two types of the immune responses, cellular and humoral, constitute a defensive barrier against various parasites and pathogens. In response to pathogens, insects produce a wide range of immune agents that act on pathogens directly, such as cecropins or lysozyme, or indirectly by the stimulation of hemocyte migration or by increasing phenoloxidase (PO) activity. Recently, many new immunologically active substances from insects, such as peptides and polypeptides, have been identified. Nevertheless, in the most cases, their physiological functions are not fully known. One such substance is yamamarin – a pentapeptide isolated from the silk mothAntheraea yamamai. This yamamarin possesses strong antiproliferative properties and is probably involved in diapause regulation. Here, we examined the immunotropic activity of yamamarin by testing its impact on selected functions of the immune system in heterologous bioassays with the beetleTenebrio molitor, commonly known as a stored grains pest. Our results indicate that the pentapeptide affects the activity of immune processes in the beetle. We show that yamamarin induces changes in both humoral and cellular responses. The yamamarin increases the activity of PO, as well as causes changes in the hemocyte cytoskeleton and stimulates phagocytic activity. We detected an increased number of apoptotic hemocytes, however after the yamamarin injection, no significant variations in the antibacterial activity in the hemolymph were observed. The obtained data suggest that yamamarin could be an important controller of the immune system inT. molitor.

scholarly journals INDOLEAMINE 2,3 DIOXYGENASE AS AN IMMUNOTHERAPEUTIC TARGET BRINGS A NEW HOPE FOR CANCER PATIENTS

2018 ◽  
Vol 4 (3) ◽  
Author(s):  
Kashif Asghar ◽  
Asif Loya
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Colorectal ◽  
Immune Escape ◽  
Mammalian Target Of Rapamycin ◽  
Tumour Microenvironment ◽  
Indoleamine 2,3 Dioxygenase ◽  
Wide Range ◽  
Ido Inhibitors

Therapeutic manipulation of immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunotherapy helps the immune system to combat against cancer. Tumour cells take an edge of immunosuppressive mechanisms and inhibit antitumour immune responses. Indoleamine 2,3 dioxygenase (IDO) is an immunosuppressive enzyme which is involved in tumour immune escape mechanism in various cancers. IDO can degrade the tryptophan into kynurenines and has an ability to enhance the immune tolerance through mammalian target of rapamycin pathway general control nonderepressible 2 (GCN2) pathway and induction of regulatory T (T-regs) cells. IDO-induced T-regs suppress the local immune responses in the tumour microenvironment and promote metastasis. IDO overexpression in various cancers is associated with poor prognosis. Several preclinical and clinical trials have been proceeding and recommend that IDO inhibitor may be an influential tool against a wide range of cancers. IDO inhibitors as adjuvant therapeutic agents may also have clinical implications. Thus, IDO has the potential to be used as an immunotherapeutic target. This review discusses the promising role of IDO in cancer and its implication in immunotherapy.Key words: Breast cancer, colorectal cancer, haematological malignancies, immunotherapy, indoleamine 2,3-dioxygenase, pancreatic cancer, prostate cancer

Ovarian cancer and inflammation. Part 1. Pro-inflammatory cytokines.

2018 ◽  
Vol 8 (1) ◽  
pp. 194-201
Author(s):  
KM. Terlikowska ◽  
MA. Strzyż-Skalij ◽  
K. Kryński ◽  
M. Osmólska ◽  
Z. Łada ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Cause Of Death ◽  
Inflammatory Cytokines ◽  
Gynecologic Malignancies ◽  
Cancer Tumor ◽  
Cancer And Inflammation ◽  
Pro Inflammatory Cytokines

Ovarian cancer is the most threatening cause of death among gynecologic malignancies and represents the fifth leading cause of death from all cancers for women. Research reveals that ovarian cancer patients exhibit significant immune responses against the tumor. In this review of the current literature chiefly the interaction of ovarian cancer tumor cells and the immune system is discussed. There is increasingly growing evidence that pro-inflammatory cytokines are involved in intricate complex of mechanisms responsible for tumorigenesis, and delicate balance between pro- and anti-inflammatory cytokines is critical for the antitumor host immune response.

Early nutritional environment: focus on health effects of microbiota and probiotics

2010 ◽  
Vol 1 (4) ◽  
pp. 383-390 ◽  
Author(s):  
K. Laitinen ◽  
M. Collado ◽  
E. Isolauri
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Health Effects ◽  
Life Style ◽  
Maternal Nutrition ◽  
Well Being ◽  
Low Grade ◽  
Critical Periods ◽  
Female Population

Balanced maternal nutrition during pregnancy ensures both the growth and development of the foetus and the well-being of the mother. Recent evidence supports the programming theory, which envisages long-lasting effects on later risk of chronic life-style-related diseases by early nutrition. The increasing problem of overweight, affecting almost half of the female population in Western societies, sets off adverse programming effects in the offspring manifested in subsequent health effects. To combat this problem, new tools involving life-style modifications are being actively sought to increment the traditional approaches. Immunonutrition, the ability of nutrients to influence the activities of cells in the immune system, may be one answer in combating low-grade systemic inflammation, the key underlying determinant in the obesity epidemic. Further, microbial compounds possess immunomodulatory properties which may be utilised to improve immune responses in clinically meaningful ways. Aberrant microbiota compositions have been detected during critical periods when early programming occurs, including pregnancy and infancy. Such alterations may regulate the health of the infant and the risk of subsequent disease, as demonstrated by the divergence in gut microbiota composition between healthy and overweight individuals. It may thus be hypothesised that the composition of the gut microbiota could be used as a target for intervention. Probiotics interact with the mucosal immune system via the same pathways as commensal bacteria to influence both innate and adaptive immune responses. In consequence, interventions with immunomodulatory diets, including certain nutrients and probiotics, may be critical in coordinating the adaptive function necessary for the formation of tolerance and thus in the prevention of undesirable metabolic consequences.

Diagnostic co-morbidity in 2300 psychiatric out-patients presenting for treatment evaluated with a semi-structured diagnostic interview

2007 ◽  
Vol 38 (2) ◽  
pp. 199-210 ◽  
Author(s):  
M. Zimmerman ◽  
J. B. McGlinchey ◽  
I. Chelminski ◽  
D. Young
Keyword(s):  
Psychiatric Disorders ◽  
Rhode Island ◽  
Present Report ◽  
Post Traumatic Stress ◽  
Principal Diagnosis ◽  
Epidemiological Surveys ◽  
Co Morbidity ◽  
Wide Range ◽  
Axis I ◽  
Dsm Iv

BackgroundThe largest clinical epidemiological surveys of psychiatric disorders have been based on unstructured clinical evaluations. However, several recent studies have questioned the accuracy and thoroughness of clinical diagnostic interviews; consequently, clinical epidemiological studies, like community-based studies, should be based on standardized evaluations. The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is the largest clinical epidemiological study using semi-structured interviews assessing a wide range of psychiatric disorders conducted in a general clinical out-patient practice. In the present report we examined the frequency of DSM-IV Axis I diagnostic co-morbidity in psychiatric out-patients.MethodA total of 2300 out-patients were interviewed with the Structured Clinical Interview for DSM-IV (SCID) upon presentation for treatment.ResultsThe mean number of current and lifetime DSM-IV Axis I disorders in the 2300 patients was 1.9 (s.d.=1.5) and 3.0 (s.d.=1.8) respectively. The majority of patients were diagnosed with two or more current disorders, and more than one-third were diagnosed with three or more current disorders. Examination of the most frequent current disorders in the patients with the 12 most common principal diagnoses indicated that the pattern of co-morbidity differed among the disorders. The highest mean number of current co-morbid disorders was found for patients with a principal diagnosis of post-traumatic stress disorder and bipolar disorder.ConclusionsClinicians should assume that psychiatric patients presenting for treatment have more than one current diagnosis. The pattern of co-morbidity varies according to the principal diagnosis.

scholarly journals Immunoceptive inference: why are psychiatric disorders and immune responses intertwined?

2021 ◽  
Vol 36 (3) ◽  
Author(s):  
Anjali Bhat ◽  
Thomas Parr ◽  
Maxwell Ramstead ◽  
Karl Friston
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Psychiatric Disorders ◽  
Message Passing ◽  
Genetic Mutations ◽  
Active Inference ◽  
Sensory Attenuation ◽  
The Brain ◽  
Neuropsychiatric Conditions

AbstractThere is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this would require a step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems?

Stress and Mental Disorders: Insights from Animal Models

2020 ◽  
Author(s):  
Richard McCarty
Keyword(s):  
Bipolar Disorder ◽  
Animal Models ◽  
Mental Disorders ◽  
Anxiety Disorders ◽  
Psychiatric Disorders ◽  
Inbred Mice ◽  
Autism Spectrum ◽  
Post Traumatic Stress ◽  
Behavioral Alterations ◽  
Dynamic Interactions

Stress has now been recognized as an important factor in the development or recurrence of various mental disorders, from major depressive disorder to bipolar disorder to anxiety disorders. Stressful stimuli appear to exert their effects by acting upon individuals with susceptible genotypes. Over the past 50 years, animal models have been developed to study these dynamic interactions between stressful stimuli and genetically susceptible individuals during prenatal and postnatal development and into adulthood. This book begins with a discussion of the history of psychiatric diagnosis and the recent goal of moving toward precision psychiatry, followed by a review of clinical research on connections between stressful stimuli and the development of psychiatric disorders. Chapters are also included on neuroendocrine, immune, and brain systems involved in responses to stress. Additional chapters focus on the development of animal models in psychiatry and the susceptibility of the developing organism to stressful stimuli. Subsequent chapters are devoted to animal models of specific stress-sensitive psychiatric disorders, including schizophrenia, autism spectrum disorders, bipolar disorder, anxiety disorders, depression, and post-traumatic stress disorder. These chapters also focus on the identification of promising molecular targets for development of new drug therapies; a chapter examines animal models of resilience to stress-induced behavioral alterations as a newer approach to understand why some animals (e.g., inbred mice) are susceptible to stress and others are resilient, even if they are essentially genetically identical. The final chapter discusses how these basic laboratory animal models are providing promising leads for future breakthroughs in the diagnosis, treatment, and prevention of mental disorders.

Sign in / Sign up

Export Citation Format

Share Document