Dietmar Fuchs

Medizinische Universität Innsbruck · Institute of Biological Chemistry

Introduction. Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systemat...

Phyllobilins are natural products derived from the degradation of chlorophyll, which proceeds via a common and strictly controlled pathway in higher plants. The resulting tetrapyrrolic catabolites—the phyllobilins—are ubiquitous in nature; despite their high abundance, there is still a lack of knowledge about their physiological properties. Phyllob...

Background Currently available medication for Alzheimer’s disease (AD) may slows cognitive decline only transitory, but has failed to bring about long term positive effects. For this slowly progressive neurodegenerative disease so far no disease modifying therapy exists. Objective To find out if non-pharmacologic non-ivasive neuromodulatory repeti...

Background: Recent research has suggested that excessive alcohol consumption in patients with alcohol use disorder (AUD) is associated with chronic immune activation, which affects the metabolism of the neurotransmitter precursor amino acid tryptophan (TRP) and contributes to the complex pathophysiology of AUD. Our study investigated possible immu...

Background Indoleamine 2,3-dioxygenase (IDO) activity is induced by cellular immune activation and therefore associated to inflammatory diseases, among others psychiatric disorders. This review aims to elucidate IDO activity reflected by kynurenine (KYN) to tryptophan (TRP) ratio in severe mental disorders. Methods A systematic literature search i...

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and...

Background The authors explore the therapeutic and prophylactic efficacies of Immunopterin (calcium pterin-6-carboxylate chelate) against coronavirus colds and as a therapy against COVID-19. Methods To determine Immunopterin’s therapeutic efficacy against colds and flus, a 5-year observational study was conducted with 34 subjects who took Immunopt...

Melatonin secretion decreases with age and in neurodegenerative diseases like Alzheimer’s Disease (AD). Sundown syndrome (“sundowning”), characterized by agitation, wandering, anxiety, aggression and confusion in the evening and at night is prevalent among demented patients [1,2]. Delirious state is a very common complication in severe dementia, dy...

Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7⁺ cDC1 expressed IDO1 that was dependent on I...

Following publication of the original article [1], an error was reported in the reference list wherein reference 20 has an incorrect journal name. Incorrect: Calcagno A, Alberione MC, Romito A, Imperiale D, Ghisetti V, Audagnotto S, et al. Prevalence and predictors of blood-brain barrier damage in the HAART era. J Neuro-Oncol. 2014;20:521–5. Correc...

Importance: Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF). Objective: To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity. Design, setting, and participants: T...

It is currently unclear whether potential probiotics such as lactic acid bacteria could affect behavioral problems in birds. To this end, we assessed whether a supplementation of Lactobacillus rhamnosus JB-1 can reduce stress-induced severe feather pecking (SFP), feather damage and fearfulness in adult birds kept for egg laying. In parallel, we ass...

Background Immune activation or high levels of stress may lead to increased metabolism of tryptophan during pregnancy. Porphyromonas gingivalis (Pg), the “keystone” periodontal pathogen, induces immune and indoleamine 2,3-dioxygenase (IDO) activation. Thus, we hypothesized that larger gestational decreases in tryptophan and elevations in neopterin...

The mechanisms of persistent central nervous system (CNS) inflammation in people with HIV (PWH) despite effective antiretroviral therapy (ART) are not fully understood. We have recently shown that plasma anti-CD4 IgGs contribute to poor CD4⁺ T cell recovery during suppressive ART via antibody-mediated cytotoxicity (ADCC) against CD4⁺ T cells, and t...

Background Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB befo...

Background: Little is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms. Methods: A 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements...

Ageing is accompanied with a decline in several physiological systems. Frailty is an age-related syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalisation, and death in older adults. The aim of this study was to understand the re...

Immune-mediated inflammatory processes and oxidative stress are involved in the aetiopathogenesis of bipolar disorder (BD) and weight-associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found to be more active in BD, and associated with over...

Background: Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH).Methods: PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt...

Anemia is very common in patients with inflammatory disorders. Its prevalence is associated with severity of the underlying disease, and it negatively affects quality of life and cardio-vascular performance of patients. Anemia of inflammation (AI) is caused by disturbances of iron metabolism resulting in iron retention within macrophages, a reduced...

Abstract In mammals, early-life probiotic supplementation is a promising tool for preventing unfavourable, gut microbiome-related behavioural, immunological, and aromatic amino acid alterations later in life. In laying hens, feather-pecking behaviour is proposed to be a consequence of gut-brain axis dysregulation. Lactobacillus rhamnosus decreases...

The naturally occurring stilbenoid oxyresveratrol was shown to influence inflammatory and metabolic processes. During cellular immune activation, tryptophan breakdown and neopterin formation via the enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and GTP-cyclohydrolase, respectively, are induced. Neopterin and the kynurenine to tryptophan ratio are r...

Feather pecking (FP) is a stress-induced neuropsychological disorder of birds. Intestinal dysbiosis and inflammation are common traits of these disorders. FP is, therefore, proposed to be a behavioral consequence of dysregulated communication between the gut and the brain. Probiotic bacteria are known to favorably modulate the gut microbiome and he...

Objective: Anemia is often found in patients with coronary artery disease (CAD) or acute coronary syndrome (ACS) and related to disease severity. Our study investigated the relationship between anemia, iron homeostasis and inflammation in CAD and examined their influence on the outcome of patients. Patients and Methods: Markers of immune activation...

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression offers an alternative therapy, since more than every third patient is not responding to adequate antidepressive treatment. In this interventional study safety, symptom development and changes of serum concentrations of neurotransmitter precursor amino acids...

The immunomodulatory capacity of mental stress is one of the basic concepts of psychoneuroimmunology. The current prospective longitudinal study was designed to evaluate the effect of acute mental stress on neurotransmitter precursor amino acid levels in individuals with depression at 2 time points. Ten physically healthy patients with a diagnosis...

Objective: Persistent immune activation in the central nervous system and systemically are common in people living with HIV (PLHIV) despite antiretroviral therapy. It is not known whether this is generated by HIV replication or other components such as coinfections and lifestyle-related factors. Design: To determine the importance of different f...

COPD and asthma are two distinct but sometimes overlapping diseases exhibiting varying degrees and types of inflammation on different stages of the disease. Although several biomarkers are defined to estimate the inflammatory endotype and stages in these diseases, there is still a need for new markers and potential therapeutic targets. We investiga...

Objectives Major depressive disorder (MDD) is associated with dysregulations of leptin and tryptophan–kynurenine (Trp–Kyn) (TKP) pathways. Leptin, a pro-inflammatory cytokine, activates Trp conversion into Kyn. However, leptin association with down-stream Kyn metabolites in MDD is unknown. Methods Fasting plasma samples from 29 acutely ill drug-na...

Objective To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. Methods This is a cross-sectional analysis of archived CS...

Background: Disclosure of one's sexual orientation as a sexual-minority (SM) person (i.e., being "out") may affect HIV-related health outcomes. This longitudinal study examined whether race/ethnicity moderated effects of outness on the plasma kynurenine/tryptophan (KT) ratio, a marker of dysregulated serotonin metabolism due to immune activation t...

The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1) has gained major attention due the immunoregulatory nature of this pathway. Both depletion of tryptophan concentrations as well as the accumulation of downstream metabolites are relevant for the mediation of the manifold consequences of increased tryptophan metabolism. Increased...

The new coronavirus SARS-CoV-2 was identified to be responsible for the COVID-19 pandemic. There are striking differences in the response to infection, some people develop no or mild symptoms, while other outcomes are severe of even fatal. For those COVID-19 patients who require hospitalization, prognostic markers could help clinicians to identify...

The microbiota–gut–brain axis plays an important role in the development of neurode- generative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated infla...

This longitudinal study with 76 sexual minority men living with HIV who use methamphetamine examined whether dysregulation of essential amino acid precursors for neurotransmitters at baseline predicted positive and negative affect at 15 months. After controlling for covariates including baseline positive affect, a higher baseline kynurenine/tryptop...

Background This study on a breast cancer survivor investigated how episodic practice of various complementary and alternative medicine (CAM) techniques affected the dynamics of emotional states and urinary neopterin—an inflammation marker. Methods The 49-year-old female patient (diagnosis: ductal breast carcinoma 5 years before study start, suffer...

Background: Metabolic profiling in non-small cell lung cancer (NSCLC) may identify key metabolic vulnerabilities and shows enormous discovery potential. Preclinical studies showed that metabolic rewiring in cancer plays an essential role in modulation of immunotherapy response. However, this situation is understudied in the clinical setting. There...

This book provides practical information about interdisciplinary research, particularly to students and researchers of animal behaviour, animal welfare and veterinary sciences, to better understand how the integration of disciplines can advance animal welfare science. The book is divided into 2 parts. Part 1 gives guidance on how interdisciplinary...

HIV infection is associated with increased systemic microbial translocation, neuro-inflammation and occasionally neuronal injury. Whether systemic LPS penetrates into the brain and contributes to neuro-inflammation remain unknown in HIV. Here, we measured plasma and cerebrospinal fluid (CSF) LPS levels along with biomarkers of neuro-inflammation (w...

Background The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS...

This study reports preliminary findings on the hypothesis that worldview can predict cardiovascular and cortisol responses to social stress. Based on theory and previous findings, we assumed that worldview security would provide a basis for stress resilience. Accordingly, religious and atheist individuals were expected to show higher stress resilie...

Background: This longitudinal study examined whether co-occurring stimulant use and HIV disease processes predicted greater risk for depression via dysregulated metabolism of amino acid precursors for neurotransmitters. Methods: In total, 110 sexual minority men (i.e., gay, bisexual, and other men who have sex with men) living with HIV who had b...

A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppres...

Anemia often coincides with depression and impaired quality of life (QoL) in cancer patients. Sustained immune activation can lead to the development of anemia. Furthermore, it also may go along with changes in tryptophan and phenylalanine metabolism. The aim of our pilot study was to study the relationship between anemia, immune-mediated changes i...

Objective: To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements. Methods: We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immu...

Background: Across many settings, lack of virologic control remains common in people with HIV (PWH) due to late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remain prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). Metho...

Within this Research Topic, 17 articles discuss new and deepen known aspects of theimmunomodulatory effects of TRP metabolites in various diseases. New mechanistic insights intothe regulation of TRP metabolism and novel signaling pathways activated by specific metabolitesare reported. In addition, possible new therapeutic and diagnostic approaches...

Background: The morbidity in dengue fever is dependent on the dengue virus (DENV) serotypes, the patient age, predisposing immunogentic markers and the frequency of primary and secondary infections. This study aims to distinguish acute primary from secondary dengue infections of Vietnamese adults and to assess the association of viremia and anti-d...

Background The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS...

Few studies have examined neuroimmune pathways that could contribute to impulsivity in people living with HIV who use substances. Eighty-four methamphetamine-using, sexual minority men with an undetectable HIV viral load were administered the Balloon Analogue Risk Task (BART), a behavioral measure of risk-taking propensity. We examined the associat...

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-...

Background People living with HIV who use stimulants, such as methamphetamine, display greater immune dysregulation and experience faster clinical HIV progression. However, it remains unclear if the extent of immune dysregulation differs between methamphetamine users who engage in injection drug use (Meth IDU) and methamphetamine users who do not....

Acute and chronic mental stress are both linked to somatic and psychiatric morbidity, however, the neurobiological pathways of these associations are still not fully elucidated. Mental stress is known to be immunomodulatory, which is one of the basic concepts of psychoneuroimmunology. In the present study, neurotransmitter precursor amino acid leve...

Background: Soluble P-selectin (sP-selectin) is associated with risk factors for cardiovascular disease (CVD) but this association has not been evaluated in patients with schizophrenia. This study primarily evaluated the association of sP-selectin with plasma lipids and nitrite (NO 2 -) respectively in overweight/obese adults with schizophrenia. Me...

Dementia is an increasing health problem in older aged populations worldwide. Age-related changes in the brain can be observed decades before the first symptoms of cognitive decline appear. Cognitive impairment has chronic inflammatory components, which can be enhanced by systemic immune activation. Mutual interferences between inflammation and cog...

The original version of this article unfortunately contained a mistake. There was an error in Fig. 2. The original article has been corrected. We apologize for the mistake. The correct Fig. 2 is given …

Background: Alzheimer's disease has chronic inflammatory components, which can be enhanced by systemic immune activation resulting in inflammation or vice versa. There is growing evidence that chronic periodontitis drives systemic inflammation and finally Alzheimer's disease. Thus, a link might exist between oral pathogens and Alzheimer's disease....

Immune activation coincides with disturbances in iron and vitamin D metabolism in patients with cardiomyopathy. In this study, we investigated whether there are differences regarding immune activation, iron and vitamin D metabolism between the different cardiomyopathy aetiologies. Patients and methods: Parameters of iron metabolism (haemoglobin, ir...

Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-infla...