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      Neopterin in Diagnosis and Monitoring of Infectious Diseases

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      Journal of biomarkers
      Hindawi Publishing Corporation

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          Abstract

          Neopterin is produced by activated monocytes, macrophages, and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes. Quantification of neopterin in body fluids has been achieved by standard high-performance liquid chromatography, radioimmunoassays, and enzyme-linked immunosorbent assays. Neopterin levels predict HIV-related mortality more efficiently than clinical manifestations. Successful highly active antiretroviral therapy is associated with a decrease in neopterin levels. Elevated neopterin levels were associated with hepatitis by hepatitis A, B, and C viruses. Serum neopterin levels were found to be a predictor of response to treatment of chronic HCV infection with pegylated interferon combined with ribavirin. Neopterin levels of patients with pulmonary tuberculosis were found to be higher in patients with more extensive radiological changes. Elimination of blood donors with elevated neopterin levels to reduce risk of transmission of infections with known and unknown viral pathogens has been undertaken. Neopterin measurement is hereby more cost effective but less sensitive than screening using polymerase chain reaction based assays. In conclusion neopterin is a nonspecific marker of activated T-helper cell 1 dominated immune response. It may be a useful marker for monitoring of infectious disease activity during treatment and for more accurate estimation of extent of disease and prognosis.

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          Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma

          Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response- associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.
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            Potential role of immune system activation-associated production of neopterin derivatives in humans.

            Neopterin derivatives are produced by human monocyte-derived macrophages and dendritic cells upon stimulation with interferons. Neopterin concentrations measured in urine or blood reflect activation of cellular immunity and endogenous release of interferon-gamma. This review focuses on the clinical utility of measuring neopterin levels in inflammatory disease and the potential functions of neopterin as a mediator and/or modulator in the course of inflammatory and infectious processes. In vitro-studies revealed that neopterin derivatives exhibit distinct biochemical effects, most likely via interactions with reactive oxygen or nitrogen intermediates, thereby affecting the cellular redox state. Data support the hypothesis that the release of neopterin enhances the cytotoxic potential of activated macrophages and dendritic cells. In vivo, a strong correlation between neopterin levels and the severity, progression, and outcome of infectious and inflammatory diseases was found. The influence of neopterin derivatives on the cellular metabolism may provide an explanation for these clinical observations.
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              The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases.

              The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.
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                Author and article information

                Journal
                J Biomark
                J Biomark
                JBM
                Journal of biomarkers
                Hindawi Publishing Corporation
                2090-8660
                2090-7699
                2013
                8 December 2013
                : 2013
                : 196432
                Affiliations
                Paediatric Department, Luton and Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton LU40DZ, UK
                Author notes

                Academic Editor: Yvan Devaux

                Article
                10.1155/2013/196432
                4437389
                26317013
                487c2592-4669-4b84-8dde-17f4fae997d6
                Copyright © 2013 Michael Eisenhut.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 August 2013
                : 28 October 2013
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                Review Article

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