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

Huber, Ch.; Batchelor, J. R.; Fuchs, Dietmar; Hausen, Arno; Lang, Alois; Niederwieser, Dietger; Reibnegger, Gilbert; Swetly, Peter; Troppmair, Jakob; Wächter, Helmut

doi:10.1084/jem.160.1.310

Cited by 1,011 publications

(482 citation statements)

References 11 publications

Supporting

Mentioning

447

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, PCNSL tumor cells can secrete monocyte chemoattractant proteins which may induce the secretion of Npt from monocytes‐macrophages 30. Several studies have also reported that B lymphocytes can secrete Npt 31, 32. In the present study, we found that the CSF Npt concentration in patients with PCNSL was significantly higher than that in patients with other brain tumors and inflammatory diseases.…”

Section: Discussionsupporting

confidence: 57%

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

et al. 2018

View full text Add to dashboard Cite

This study aimed at evaluating the diagnostic and prognostic role of neopterin (Npt) concentration in the cerebrospinal fluid (CSF) of patients with primary central nervous system lymphoma (PCNSL). Ninety‐nine patients were enrolled in this retrospective study; these included patients with PCNSL (n = 21), other brain tumors (n = 44), and inflammatory diseases (n = 34). CSF Npt concentration was measured using ELISA. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminative ability of CSF Npt concentration for the diagnosis of PCNSL. CSF Npt concentration in patients with PCNSL was significantly higher than that in patients with other brain tumors and inflammatory diseases (P < .001). On ROC curve analysis, the optimal cutoff CSF Npt level of 10.77 ng/mL for the diagnosis of PCNSL and the diagnostic yield of MRI were increased when used in conjunction with CSF Npt concentration. The CSF Npt concentrations in PCNSL patients with multiple lesions were significantly higher than those in patients with a single lesion. Changes in CSF Npt concentration were consistent with post‐treatment changes in tumor sizes. The CSF Npt concentration may be a good biomarker for the diagnosis, for monitoring of disease course, and for prognostic evaluation of patients with PCNSL.

show abstract

Section: Discussionsupporting

confidence: 57%

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In this respect, our finding that circulating neopterin concentrations were higher in the vitamin A-deficient infants is intriguing. It is generally believed that elevated neopterin concentrations reflect increased macrophage activity, and this is regulated by IFN-g (Huber et al, 1984). How can this paradox of decreased ex vivo IFN-g production and increased in vivo neopterin concentrations be explained?…”

Section: Discussionmentioning

confidence: 99%

Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants

et al. 2004

View full text Add to dashboard Cite

Objective: To determine effects of vitamin A, zinc and iron deficiency in Indonesian infants on the ability to produce immunoregulatory cytokines. Design, setting and subjects: Immunological asssessment was done in 59 infants participating in a cross-sectional nutritional survey in rural West Java, Indonesia. Production of T-helper cell type-1 (Th1, cell-mediated) cytokines interferon-g (IFN-g), interleukin-12 (IL-12), interleukin-18 (IL-18) and T-helper cell type-2 (Th2, humoral) cytokine interleukin-6 (IL-6) were measured after stimulation with lipopolysaccharide and phytohemagglutinin in an ex vivo whole blood culture system. Circulating neopterin concentrations were determined as an indicator of in vivo macrophage activity. Results: Of the infants, 48% were vitamin A deficient, 44% were anemic (with 17% having iron deficiency anemia), and 17% were zinc deficient. Vitamin-A deficient infants had significantly reduced ex vivo production of IFN-g, but also significantly higher circulating neopterin concentrations. Production of IFN-g and IL-12 were strongly correlated, IFN-g and IL-18 production were not. Zinc deficiency was accompanied by significantly reduced white blood cell counts and reduced ex vivo production of IL-6. Iron status was not related to cytokine production. Conclusions: This study shows that in vitamin A deficiency there is Th1 dominance in a steady state, combined however with impairment of the Th1 response after stimulation, whereas in zinc deficiency, there is a decreased Th2 response. Overall, vitamin A deficiency and zinc deficiency have marked albeit different effects on the immunocompetence of infants, affecting both cellmediated and humoral components of the immune system.

show abstract

“…IDO induction is generally believed to represent a feedback mechanism of APC activation [8]. This understanding is supported by the observation that neopterin, a guanosine triphosphate (GTP) cleavage product [13], has been found to be closely linked to IDO activity in a wide spectrum of conditions involving immune activation [14][15][16].In some recent reports, also prostaglandin E2 (PGE 2 ) was described to up-regulate IDO competence in human DCs [17,18]. Induction of IDO competence through PGE 2 occurred, like in human DC maturation [19,20], in concert with TNF-α.…”

mentioning

confidence: 95%

Ambivalent effects of dendritic cells displaying prostaglandin E2‐induced indoleamine 2,3‐dioxygenase

et al. 2012

View full text Add to dashboard Cite

Prostaglandin E2 (PGE 2 ), an abundantly produced lipid messenger in mammalian organisms, has been attributed to possess potent albeit ambivalent immunological functions. Recently, PGE 2 has been reported to stimulate the commonly believed immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway in human dendritic cells (DCs), but without promoting DC immunosuppressive activity. Here, we report that PGE 2 used as a DC maturation agent apparently has more diverse functions. PGE 2 -matured DCs acquired powerful IDO activity, which was sustained even after removing PGE 2 . These IDO-competent DCs were able to stimulate allogeneic T-cell proliferation, but achieved inhibitory activity as their content in DC/T-cell co-cultures increased. The DC inhibitory activity was reversed upon blockade of IDO activity, confirming that the suppressive effect was in fact mediated by IDO and occurred in a dose-dependent fashion. IDO-mediated T-cell suppression was restored upon re-stimulation of T cells in the absence of IDO activity, confirming its reversibility. T cells stimulated by PGE 2 -matured IDO-competent DCs were sensitized to produce multiple cytokines, comprising Th1, Th2, and Th17 phenotypes. Collectively, these data suggest that T cells stimulated by PGE 2 -matured DCs are not terminally differentiated and their ultimate type of response may be formed by microenvironmental conditions. Keywords: Human dendritic cells r IL-23 r Immunosuppression r Indoleamine 2,3-dioxygenase (IDO) r Prostaglandin E2 Supporting Information available online IntroductionThe intracellular enzyme indoleamine 2,3-dioxygenase (IDO) has a key function in tryptophan metabolism along the kynurenine pathway [1]. IDO's metabolic activity has been perceived to play a significant role in immune regulation. On the cellular level, the complementary effects of IDO-mediated metabolism, tryptophan starvation, and accumulation of immunomodulatory kynurenines Correspondence: Dr. Andreas Heitger e-mail: andreas.heitger@ccri.at at the antigen-presenting cell (APC)/T-cell synapse were proposed to effect regulation of T-cell activation and proliferation [1,2]. In fact, in the last decade, multiple studies corroborated the role of IDO in immune regulation and induction of tolerance (reviewed in [3,4]). IDO competence, i.e. IDO expression and activity [5,6], has been suggested to play a critical role in numerous clinical conditions entailing immune regulation, including tolerance induction in pregnancy [7], transplantation [8,9], and tumor immune evasion [10]. * These authors contributed equally to the work. Eur. J. Immunol. 2012Immunol. . 42: 1117Immunol. -1128 Effective induction of IDO competence is, by and large, restricted to cells of the monocyte/macrophage lineage and, in humans is predominantly found in dendritic cells (DCs) [4,11]. Numerous agents, most prominently interferon (IFN)-γ, have been described to induce IDO activity in DCs [12]. IDO induction is generally believed to represent a feedback mechanism of APC activation [8]. This understanding...

show abstract

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

Cited by 1,011 publications

References 11 publications

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants

Ambivalent effects of dendritic cells displaying prostaglandin E2‐induced indoleamine 2,3‐dioxygenase

Contact Info

Product

Resources

About