Neopterin to Monitor Clinical Pathologies Involving Interferon-γ Production

Pteridines ◽  
2004 ◽  
Vol 15 (3) ◽  
pp. 75-90 ◽  
Author(s):  
Katharina Schroecksnadel ◽  
Christian Murr ◽  
Christiana Winkler ◽  
Barbara Wirleitner ◽  
Lothar C. Fuith ◽  
...  
Keyword(s):  
Malignant Tumor ◽  
Reactive Oxygen ◽  
Hiv Infections ◽  
Interferon Γ ◽  
Prognostic Information ◽  
Tumor Diseases ◽  
Survival Expectations ◽  
Diagnostic Applications ◽  
The Moment ◽  
Cellular Immune

Abstract Upon stimulation with the cytokine interferon-γ human monocytes/macrophages produce neopterin. Accordingly, measurement of neopterin concentrations in body fluids like blood, urine or cerebrospinal fluid provides information about activation of immune response involving type 1 Τ helper cells. Increased neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes, but also in some neurodegenerative and in cardiovascular diseases. Major diagnostic applications of neopterin measurements are monitoring of the immune status of allograft recipients, detection of infectious diseases in blood donations and monitoring of therapy in HIV-infected individuals. Neopterin concentrations also provide prognostic information in HIV-infected individuals and in several malignant tumor diseases, high neopterin production at the moment of diagnosis is associated with poorer survival expectations. As high neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like α-tocopherol, neopterin can be regarded as a marker of oxidative stress caused by an activated immune system. Therefore, by neopterin measurements not only the extent of cellular immune activation, but also the extent of tissue damage caused by reactive oxygen specics may be estimated.

The Importance of Neopterin as a Laboratory Diagnostic Marker of Immune Activation

Pteridines ◽  
1999 ◽  
Vol 10 (3) ◽  
pp. 101-111 ◽  
Author(s):  
Bernhard Widner ◽  
Christian Murr ◽  
Barbara Wirleitner ◽  
Christiane Mayr ◽  
Nathalie Spöttl ◽  
...  
Keyword(s):  
Immune Activation ◽  
Viral Infections ◽  
Diagnostic Marker ◽  
Hiv Infections ◽  
Intracellular Bacteria ◽  
Therapy Control ◽  
Blood Banks ◽  
Diagnostic Applications ◽  
Cellular Immune

Summary Neopterin is produced and secreted in large amounts by interferon-g stimulated human monocytes/macrophages. Neopterin measurement in urine and semm provides a usefi.ll possibility to estimate the dcgree of ccllular (Thl-type) immune activation, which is directed against viral infections, intracellular bacteria, and certain parasites. Also in malignancy, autoimmw1e diseases and allograft rejection episodes neopterin sensitively reflects the extent of cellular immune activation. Determination of neoptcrin concentrations can be conveniently performed by immunoassay like ELISA or RIA, and HPLC. The major diagnostic applications of neopterin monitoring are: surveillancc of the immw1e status of organ recipients, therapy control and prognosis of diseasc progression in tumor diseascs and HIV infections and also detection of unknown infections in e.g. blood banks. High neopterin levels are strongly associated with oxidative stress, opening an additional application field of ncopterin monitoring to estimate the extent of tissue damagc in the course of immune activation.

scholarly journals IDO-Mediated Tryptophan Degradation in the Pathogenesis of Malignant Tumor Disease

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4157 ◽  
Author(s):  
Robert Sucher ◽  
Katharina Kurz ◽  
Guenter Weiss ◽  
Raimund Margreiter ◽  
Dietmar Fuchs ◽  
...  
Keyword(s):  
Malignant Tumor ◽  
Immune Escape ◽  
Interferon Γ ◽  
Immune Defense ◽  
Tumor Diseases ◽  
Biochemical Pathways ◽  
Tryptophan Degradation ◽  
Long Run ◽  
Ifn Γ ◽  
Tryptophan Catabolites

Immune escape is a fundamental trait of cancer in which the Th1-type cytokine interferon-γ (IFN-γ) seems to play a key role. Among other tumoricidal biochemical pathways, IFN-γ induces the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in a variety of cells including macrophages, dendritic cells (DCs) and tumor cells. IDO activity has been shown to reflect the extent and the course in a plethora of malignancies including prostate, colorectal, pancreatic, cervical, endometrial, gastric, lung, bladder, ovarian, esophageal and renal cell carcinomas, glioblastomas, mesotheliomas, and melanomas. Furthermore IDO activity during malignant tumor diseases seems to be part of the tumoricidal immune defense strategy, which in the long run is detrimental to the host, when tryptophan deprivation and production of pro-apoptotic tryptophan catabolites counteract T-cell responsiveness.

scholarly journals Stratification by interferon-γ release assay level predicts risk of incident TB

Thorax ◽  
2018 ◽  
Vol 73 (7) ◽  
pp. 652-661 ◽  
Author(s):  
Brita Askeland Winje ◽  
Richard White ◽  
Heidi Syre ◽  
Dag Harald Skutlaberg ◽  
Fredrik Oftung ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Risk Model ◽  
Large Population ◽  
Interferon Γ ◽  
National Registry ◽  
Routine Practice ◽  
Prescription Database ◽  
Prognostic Information ◽  
Increased Risk ◽  
Ifn Γ

IntroductionTargeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting.MethodsIn this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model.ResultsThe prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL).ConclusionsConsistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Modulatory effects of interferon-γ and interleukin-4 on cellular immune responses againstHypoderma lineatumantigens

2016 ◽  
Vol 30 (4) ◽  
pp. 439-443
Author(s):  
E. CABANELAS ◽  
C. M. LÓPEZ ◽  
P. DÍAZ ◽  
A. PÉREZ -CREO ◽  
P. MORRONDO ◽  
...  
Keyword(s):  
Immune Responses ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Resolution of a chronic viral infection after interleukin-10 receptor blockade

2006 ◽  
Vol 203 (11) ◽  
pp. 2461-2472 ◽  
Author(s):  
Mette Ejrnaes ◽  
Christophe M. Filippi ◽  
Marianne M. Martinic ◽  
Eleanor M. Ling ◽  
Lisa M. Togher ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Neutralizing Antibody ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Lymphocytic Choriomeningitis ◽  
Persistently Infected ◽  
Functional Inactivation ◽  
Cellular Immune

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α− DC numbers were not affected. CD8α− DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10–mediated immune suppression, preventing IL-10 priming by CD8α− DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

scholarly journals Vitamin C and Sepsis

2021 ◽  
Author(s):  
Adriana Françozo de Melo ◽  
Giulia Oliveira Timo ◽  
Mauricio Homem-de-Mello
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Ascorbic Acid ◽  
Vitamin C ◽  
High Dose ◽  
Supportive Treatment ◽  
Tnf Α ◽  
The Moment ◽  
Cellular Immune ◽  
Very High

Vitamin C is a supplement used orally by several people globally. It may help in many other conditions, like sepsis, which is caused by an infection that leads to an imbalanced immune response involving pro (e.g., TNF-α, IL-1, IL-2, IL-6) and anti-inflammatory (e.g., IL-10, IL-4, IL-7) cytokines. Ascorbic acid is an antioxidant and acts against reactive oxygen species. At the same time, this vitamin influences cellular immune signaling, avoiding exacerbated transcription of pro-inflammatory cytokines. Very high intravenous doses have already shown to be beneficial in septic patients. Some clinical trials are still running to evaluate the real impact of vitamin C in this condition. To the moment, the combination of low-dose corticosteroids, high-dose parenteral ascorbate, and thiamine seems to be the most effective supportive treatment that could help septic patients recover.

scholarly journals Cathepsins and Their Endogenous Inhibitors in Host Defense During Mycobacterium tuberculosis and HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Elsa Anes ◽  
José Miguel Azevedo-Pereira ◽  
David Pires
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Pathogen ◽  
Hiv Infections ◽  
Pathogen Transmission ◽  
Host Cells ◽  
Chronic Infections ◽  
Host Immune Responses ◽  
Endogenous Inhibitors ◽  
Innovative Therapies ◽  
The Moment

The moment a very old bacterial pathogen met a young virus from the 80’s defined the beginning of a tragic syndemic for humanity. Such is the case for the causative agent of tuberculosis and the human immunodeficiency virus (HIV). Syndemic is by definition a convergence of more than one disease resulting in magnification of their burden. Both pathogens work synergistically contributing to speed up the replication of each other. Mycobacterium tuberculosis (Mtb) and HIV infections are in the 21st century among the leaders of morbidity and mortality of humankind. There is an urgent need for development of new approaches for prevention, better diagnosis, and new therapies for both infections. Moreover, these approaches should consider Mtb and HIV as a co-infection, rather than just as separate problems, to prevent further aggravation of the HIV-TB syndemic. Both pathogens manipulate the host immune responses to establish chronic infections in intracellular niches of their host cells. This includes manipulation of host relevant antimicrobial proteases such as cathepsins or their endogenous inhibitors. Here we discuss recent understanding on how Mtb and HIV interact with cathepsins and their inhibitors in their multifactorial functions during the pathogenesis of both infections. Particularly we will address the role on pathogen transmission, during establishment of intracellular chronic niches and in granuloma clinical outcome and tuberculosis diagnosis. This area of research will open new avenues for the design of innovative therapies and diagnostic interventions so urgently needed to fight this threat to humanity.

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