Plasma Concentrations Of Neopterin Research Articles

Neopterin production in relation to COVID-19 in the Haut-Ogooué Province, Gabon

BackgroundIn sub-Saharan Africa, understanding of the immune process associated with the COVID-19 pandemic remains scarce. This study aimed to investigate the relationship between plasma neopterin concentrations and COVID-19 infection, focusing on changes over time and age-related changes in immune response.MethodsA retrospective case study was conducted during the first wave of COVID-19 from March to August 2020. Whole blood and associated symptoms and comorbidities were collected from patients of all ages and sexes. Concentrations of plasma neopterin were measured using a commercial competitive neopterin ELISA (Neopterin ELISA, IBL International GmbH, Germany).ResultsWe analyzed data for 325 patients: 38% (n = 124) with COVID-19, and 62% (n = 201) without COVID-19, as a control group. We found that plasma neopterin concentrations were significantly higher in the COVID-19 group (mean value 45.1 nmol/L (SD 19)) than in the control group (mean value 33.8 nmol/L (SD 13)) (p = 0.004). In addition, neopterin levels decreased gradually over time in patients with COVID-19 (p < 0.001). Moreover, ROC analysis found that the best cut-off value for diagnosing COVID-19 patients based on plasma neopterin levels was 38.85 nmol/L with 70% sensitivity and 82% specificity (AUC, 0.74 [0.69–0.82], p < 0.05). We also found an increase in neopterin production with increasing age (p < 0.001).ConclusionOur findings contribute to our growing understanding of neopterin levels as a promising biomarker for the detection of COVID-19 cases in sub-Saharan Africa.

Neopterin derivatives - a novel therapeutic target rather than biomarker for atherosclerosis and related diseases.

This review provides an updated overview of the emerging roles of neopterin derivatives in atherosclerosis. Neopterin, a metabolite of guanosine triphosphate, is produced by interferon-γ-activated macrophages and is expressed at high levels in atheromatous plaques within the human carotid and coronary arteries as well as in the aorta. Plasma concentrations of neopterin are higher in patients with carotid, cerebral, and coronary artery diseases as well as aortic aneurysm. The concentration of neopterin is positively correlated with the severity of coronary artery disease. However, a prospective cohort study showed that neopterin contributes to protection against plaque formation in carotid arteries in patients with atherosclerosis. Moreover, using both in vitro and in vivo experiments, a recent study has shown the atheroprotective effects of neopterin. Neopterin suppresses the expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in endothelial cells, and thereby suppresses the adhesion of monocytes to endothelial cells. It also suppresses the inflammatory phenotype of monocyte-derived macrophages. In addition, neopterin suppresses oxidized low-density lipoprotein-induced foam cell formation in macrophages and the migration and proliferation of vascular smooth muscle cells. Neopterin injection into apolipoprotein E-deficient (Apoe-/-) mice suppresses the development of atherosclerotic lesions. A neopterin derivative tetrahydroneopterin (BH4), also known as a cofactor for nitric oxide (NO) synthases, suppresses atherosclerosis and vascular injury-induced neointimal hyperplasia in Apoe-/- mice. BH4 administration improves endothelial dysfunction in patients with coronary artery disease. These findings suggest that neopterin production may increase to counteract the progression of atherosclerosis, as neopterin contributes to atheroprotection. Otherwise, the increased neopterin levels in atherosclerosis may reflect a compensatory mechanism associated with inducible NO synthase upregulation in macrophages to supply BH4 for high output NO production caused by decreased endothelial NO synthase in atherosclerosis. Therefore, neopterin derivatives are a novel therapeutic target for atherosclerosis and related diseases.

Two types of poor immunological responder showing distinct responses to long-term HAART

ObjectivesMost previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. MethodsThis study was designed as an ambispective cohort study, including a 4–5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4–5 years and 6–7 years following HAART initiation. ResultsPIRs were subdivided into two populations after 4–5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4+ T cells and CD31+ naïve CD4+ T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. ConclusionsThe two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART.

Immunological alterations in frail older adults: A cross sectional study.

Frailty is a progressive physiologic decline in multiple body systems, characterized by loss of function, loss of physiologic reserve, and increased vulnerability to disease and death. This condition is induced by a complex and multifactorial interaction between genetic, biological, physical, psychological and environmental factors. To understand the interplay between the age-related decline of the immune response, and the upregulation of the inflammatory response, the so called inflammaging, we investigated the role of different inflammatory mediators on frailty status in the elderly. The study was performed in a population of 180 older adults (≥65 years), who were classified according to Fried's frailty phenotype. Plasma concentrations of neopterin, tryptophan, kynurenine, phenylalanine, tyrosine as well as kynurenine/tryptophan (Kyn/Trp) and phenylalanine/tyrosine (Phe/Tyr) ratios were analyzed as immune stimulation biomarkers. In addition, nitrite and C-reactive protein levels were measured as indicators of nitric oxide production and acute inflammation, respectively. Significant increases in neopterin, C-reactive protein and Kyn/Trp ratio, and decreases in tryptophan and nitrite concentrations in frail individuals compared with non-frail group were found. Both Kyn/Trp and Phe/Tyr ratios were significantly and positively correlated with neopterin. A positive correlation between kynurenine and tryptophan was also observed. Four parameters, i.e., neopterin, tryptophan, nitrite and C-reactive protein, were found to be strongly related to frailty status, although only nitrite confirmed its role of predictor after multiple regression analysis, supporting its use as a potential biomarker of frailty. Further investigation is required to strengthen the consistence and reproducibility of these findings, and to establish this parameter as a clinical biomarker of frailty.

CD16-expressing monocytes correlate with arterial stiffness in HIV-infected ART-naïve men

ObjectivesTo determine the association of the markers of monocyte activation and arterial stiffness among HIV-infected antiretroviral therapy (ART)-naïve men.MethodsSixty HIV-infected ART-naïve men and 20 HIV-uninfected male controls without symptoms or history of cardiovascular disease were recruited. Pulse wave velocity (PWV) were used as the marker of arterial stiffness and determined using a pulse pressure analyzer. The percentage of CD16-expressing monocytes was used as a marker of monocyte activation. Plasma neopterin concentration, one of the monocyte/macrophage activation markers and plasma tissue factor (TF), the coagulation marker in response to inflammatory stimuli, were also analyzed. Multivariate analyses were used to explore the association of the percentage of CD16-expressing monocytes with arterial stiffness in HIV-infected men.ResultsHIV-infected ART-naïve men demonstrated significantly higher PWV (1252.8 ± 161.6 vs.1159.2 ± 108.3 cm/s, p = 0.018). The percentage of CD16-expressing monocytes was significantly higher in HIV-infected men comparing male controls (23.4 ± 6.0% vs. 19.6 ± 4.6%, p = 0.012). Plasma concentrations of neopterin (0.91 vs. 0.64 ng/ml), p < 0.001) and TF (5.29 vs. 4.43 pg/ml, p = 0.04) were higher in HIV-infected men comparing controls. In the multivariate model for PWV among HIV-infected men, the percentage of CD16-expressing monocytes (p = 0.023) and age (p = 0.017) were significantly associated with PWV. HIV viral load, CD4 count, percentage of CD8+CD38+T cells and percentage of CD8+HLA-DR+ T cells were not associated with PWV.DiscussionHigher level of monocyte activation marker is associated with higher level of arterial stiffness in ART naïve HIV-infected men. HIV viral load, CD4 count, and the markers of CD8 T cell activation were unrelated to PWV.

Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation.

During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone. We found that mid gestation is characterized by reduced antigen-specific T cell responses associated with (1) predominance of effector memory over other T cell subsets; (2) upregulation of inhibitory markers (programmed death ligand 1); (3) heightened response to progesterone (PIBF); and (4) reduced proportions of myeloid DC and concurrent IDO activity (KTR). Conversely, antigen-specific T cell responses normalized in late pregnancy and were associated with increased markers of T cell activation (CD38, neopterin). However, these changes occur with a simultaneous upregulation of immune suppressive mechanisms including apoptosis (CD95), coinhibition (TIM-3), and immune regulation (IL-10) through the course of pregnancy. Together, our data suggest that immune tolerance dominates in the second trimester and that it is gradually reversed in the third trimester in association with immune activation as the end of pregnancy approaches.

Concentrations of neopterin, biopterin, and cortisol associated with surgical castration of piglets with lidocaine

The effect of surgical castration with local anesthesia using lidocaine on neopterin, biopterin, and cortisol blood plasma concentrations in piglets was studied. Three groups of 12 piglets were investigated: one group castrated without lidocaine, one group castrated with lidocaine, and one group left as an uncastrated control group handled in the same way as castrated piglets. Blood samples were collected 4 min before castration, and 1 h and 24 h after castration. The time × treatment interaction (P < 0.01) was detected for neopterin concentrations, yielding the result that neopterin was higher (P < 0.01) in castrated piglets without lidocaine 1 h after surgical castration compared with all other groups. The time effect (P < 0.05) was detected for biopterin concentrations. The time × treatment interaction (P < 0.01) was detected for plasma cortisol concentrations, yielding the result that neopterin was higher (P < 0.01) in castrated piglets without lidocaine and in castrated piglets with lidocaine 1 h after surgical castration compared with pre-treatment and concentrations 24 h after surgical castration. The study showed that the use of lidocaine for the surgical castration of piglets may significantly influence the activation of the immune system. This is corroborated by a significant difference in blood plasma neopterin concentrations between piglets castrated with anesthesia and those castrated without it. The use of lidocaine had no effect on cortisol concentrations in comparison with the group castrated without lidocaine.

Neopterin plasma concentrations in patients with aneurysmal subarachnoid hemorrhage: correlation with infection and long-term outcome.

OBJECT Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high rates of mortality and morbidity. The main predictor for the poor outcome is the World Federation of Neurosurgical Societies (WFNS) scale. However, this scale does not take into account proinflammatory events, such as infection occurring after the aSAH, which could modify the long-term status of patients. The aim of this study was to evaluate neopterin as an inflammatory biomarker for outcome and infection prediction in aSAH patients. METHODS Plasma concentrations of neopterin were measured in 61 aSAH patients (22 male and 39 female; mean age [± SD] 52.8 ± 11.8 years) using a commercial ELISA kit. Samples were collected daily for 10 days. Outcome at 12 months was determined using the Glasgow Outcome Scale (GOS) and dichotomized as poor (GOS score 1, 2, or 3) or good (GOS score 4 or 5). Infection was determined by the presence of a positive bacterial culture. RESULTS Patients with poor outcome at 12 months had higher concentrations of neopterin than patients with good outcome. In the same way, patients who had an infection during the hospitalization had significantly higher concentrations of neopterin than patients without infection (p = 0.001). Moreover, neopterin concentrations were significantly (p < 0.008) elevated in infected patients 2 days before infection detection and antibiotic therapy. CONCLUSIONS Neopterin is an efficient outcome predictor after aSAH. Furthermore, it is able to differentiate between infected and uninfected patients as early as 2 days before clinical signs of infection, facilitating earlier antibiotic therapy and better management.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

ObjectiveTo evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity. MethodsSixty patients diagnosed as active JIA, as well as another 60 apparently healthy age‐ and gender‐matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS‐27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C‐reactive protein. Serum concentrations of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1), and neopterin were measured. ResultsSignificant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF‐α, IL‐6, and MCP‐1 (p<0.05). A statistically significant higher mean level serum neopterin concentration (p<0.05) was found in JIA patients (20.43±8.73 nmol/L) than in controls (6.88±2.87 nmol/L) (p<0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF‐α, IL‐6, MCP‐1, and JADAS‐27 (p<0.05). No correlation was found between serum neopterin and CRP (p>0.05). Multiple linear regression analysis showed that JADAS‐ 27 and ESR were the main variables associated with serum neopterin in JIA patients (p<0.05). ConclusionThe elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

ObjectiveTo evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity. MethodsSixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured. ResultsSignificant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-α, IL-6, and MCP-1 (p<0.05). A statistically significant higher mean level serum neopterin concentration (p<0.05) was found in JIA patients (20.43±8.73 nmol/L) than in controls (6.88±2.87 nmol/L) (p<0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-α, IL-6, MCP-1, and JADAS-27 (p<0.05). No correlation was found between serum neopterin and CRP (p>0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p<0.05). ConclusionThe elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

Neopterin and biopterin as biomarkers of immune system activity associated with crating in broiler chickens

Neopterin and biopterin belong to a group of unconjugated pterin derivates. These biomolecules are present in many animal species and perform several functions. Pterin concentrations may provide additional information on the effect of stress on immune system activity. This study focused on an investigation of the effect of crating on plasma concentrations of neopterin and biopterin in broilers. The effects of 2 crating periods (2 and 4 h) were monitored in Hubbard broilers (n = 90) aged 42 d. After a given crating period, randomly selected chickens from each group were sampled immediately and the remaining chickens were sampled after 24 h. Plasma corticosterone increased (P < 0.001) immediately after 2 and 4 h crating, but no difference between the crated and the control noncrated broilers was found 24 h later. Immediately after crating, neopterin in 2- and 4-h broilers did not differ from the control, but 24 h later a decrease (P = 0.011) in plasma neopterin was found in 4-h broilers compared with the control. Simultaneously, 24 h after crating, neopterin levels in 2- and 4-h broilers decreased (P < 0.001) in comparison with the levels immediately after crating. Plasma biopterin was higher (P < 0.001) in 4-h broilers than in the control immediately after the crating. A time of sampling effect (P = 0.016) was found for the heterophil-to-lymphocyte ratio, with heterophil-to-lymphocyte ratio higher 24 h after crating in comparison with its level immediately after the crating. This study shows that crating may significantly affect the immune system of broiler chickens. This is corroborated by the increase in plasma biopterin concentrations in broilers immediately after crating and the decrease in plasma neopterin concentrations in broilers 24 h after crating. The correlations were found for widely used indicators of acute and chronic stress in birds [i.e., plasma corticosterone concentrations (biopterin) and the heterophil-to-lymphocyte ratio (neopterin), respectively].

Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction

The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.

Changes in selected biochemical indices, leukocyte profile, and pterins as biomarkers of immune system activity due to antipecking measures in pheasants

The physiological changes in response to beak trimming and spectacle usage as antipecking measures were monitored in 10-mo-old common pheasants (Phasianus colchicus). Short-term analysis conducted before the beginning of the laying period showed immediate increases of plasma corticosterone (P < 0.05) and lactate dehydrogenase (P < 0.001) concentrations and decrease of plasma triglycerides (P < 0.01) levels in response to both beak trimming and the application of spectacles. Beak-trimmed pheasants exhibited higher plasma corticosterone concentrations than pheasants fitted with spectacles (P < 0.001). To assess long-term changes, blood samples for biochemical (neopterin and biopterin determination) and hematological (leukocyte profile determination) examinations were taken from beak-trimmed, spectacles-fitted, and control pheasant hens housed in cages during their laying period. At the end of the laying period, hens fitted with spectacles exhibited lower concentrations of plasma neopterin (P = 0.005) and biopterin (P = 0.005) than beak-trimmed pheasant hens. Our findings suggest that the immune system was suppressed in spectacles-fitted pheasant hens as a result of chronic stress, as also indicated by the higher heterophil-to-lymphocyte ratio (P = 0.001) compared with beak-trimmed hens. Our study found a negative correlation (r = -0.31, P = 0.019) between the heterophil-to-lymphocyte ratio and plasma neopterin concentration. This study demonstrated that both beak trimming and use of spectacles are not only stressful procedures for pheasants, but long-term effects may also include a negative impact on the immune system.

Correlation between DAS-28 and neopterin as a biochemical marker of immune system activation in early rheumatoid arthritis

Objective: The objective of this study was to evaluate neopterin plasma concentrations in patients with early Rheumatoid Arthritis (RA) and correlate them with disease activity. Methods: This is a 28-month prospective study carried out on 65 individuals. There were 27 patients with early RA and 38 healthy volunteers as control group. Enzyme immunoassay was used to measure concentrations of neopterin and anti-cyclic citrullinated peptide (CCP) antibodies. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured turbidimetrically, and antinuclear antibodies (ANA) were detected by immunofluorescence. Patients with early RA disease activity were divided into 4 groups according to DAS-28 criteria. Neopterin concentrations in RA patients were compared to conventional RA diagnostic serological markers. Results: Healthy volunteers had a mean neopterin concentration of 5.63 ± 0.38 [1.36–9.93] nmol. L− 1. A statistically significant elevation of neopterin mean concentration was found on early RA patients: mean value of 8.92 ± 0.93 [3.94–28.3] nmol. L− 1 (p < 0.001). Pearson product moment correlation suggests a correlation between neopterin concentrations and DAS-28 (r = 0.208, p = 0.065). The analysis of the mean values grouped according with the DAS-28 criteria showed a correspondence between these means, with a Pearson correlation coefficient r = 0.979, p = 0.021. CRP concentrations also showed a similar trend. Anti-CCP antibodies and RF revealed a positive relationship with RA activity. Such a correlation was not found with ANA results. Conclusions: The elevation of plasma neopterin concentrations in early RA patients may indicate stimulation of immune response. Good correlation between neopterin concentrations and DAS-28 may facilitate assessing disease activity.

Asymmetric Dimethylarginine Concentrations Decrease in Patients with HIV Infection under Antiretroviral Therapy

In HIV-infected patients, elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor and cardiovascular risk factor asymmetric dimethylarginine (ADMA) are documented, and levels correlate with markers of immune activation, such as neopterin. In this study, the effect of antiretroviral therapy (ART) on arginine, ADMA and symmetric dimethylarginine (SDMA) levels was investigated and related to changes of immune activation markers and lipids. Concentrations of ADMA, SDMA, arginine, C-reactive protein (CRP) and neopterin were determined in 112 HIV-infected patients after 12 months of successful ART, as reflected by undetectable HIV RNA levels, and compared to baseline levels. ADMA, SDMA, arginine and urine neopterin levels were determined by HPLC, and plasma neopterin concentrations by ELISA. Disease activity before and after treatment was monitored by determination of HIV RNA levels and CD4(+) T-cell counts. Lipids and CRP were determined by routine laboratory assays. Under treatment with ART, concentrations of ADMA, SDMA and arginine dropped in parallel with decreasing HIV RNA levels and neopterin concentrations, while cholesterol, triglyceride levels and CD4(+) T-cell counts increased. CRP levels did not change. After ART, a significant inverse association between ADMA and plasma cholesterol was observed. Successful ART, defined by HIV RNA levels below the limit of detection, leads to decreasing levels of methylated arginines and immune activation markers. Thus, it is unlikely that disturbances of dimethylarginine metabolism account for the increased risk of cardiovascular events of HIV-infected patients under ART.

Assessment of Immunotoxicity Parameters in Individuals Occupationally Exposed to Lead

Although adverse health effects produced by lead (Pb) have long been recognized, studies regarding the immunotoxic effects of occupational exposure report conflicting results. In a previous study, alterations in some immunological parameters were noted in 70 Pb-exposed workers. In view of these results, it was of interest to extend this study comprising a larger population and increasing the number of immunological endpoints assessed. Accordingly, in this study the immunotoxic effects of occupational exposure to Pb were assessed by analyzing (1) percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD56+/16+); (2) concentration of plasma cytokines, namely, interleukin (IL) 2, IL4, IL6, IL10, tumor necrosis factor (TNF) α, and interferon (IFN) γ; and (3) plasma concentrations of neopterin, tryptophan (Trp), and kynurenine (Kyn). In addition, the possible influence of genetic polymorphisms in the vitamin D receptor (VDR) and δ-aminolevulinic acid dehydratase (ALAD) genes on immunotoxicity parameters was studied. Exposed workers showed significant decreases in %CD3+, %CD4+/%CD8+ ratio, IL4, TNFα, IFNγ, and Kyn to Trp ratio (Kyn/Trp), and significant increases in %CD8+, IL10, and Trp levels. All these parameters, except Trp, were significantly correlated with exposure biomarkers. No significant influence of genetic polymorphisms was observed. Significant correlation between Kyn/Trp and neopterin concentrations suggests an involvement of indoleamine 2,3-dioxygenase in the Trp metabolic alterations, which may contribute to some of the immune alterations observed. Results obtained suggest that occupational exposure to PB may influence the immune system by impairing several mechanisms, which might ultimately produce deregulation of the immune response and diminish immunosurveillance in exposed individuals.

Relationship Between Plasma Neopterin and High Sensitivity C-Reactive Protein Levels and Circadian Rhythm of Blood Pressure in Hypertensive Patients with Obstructive Sleep Apnea Syndrome

To investigate the relationship between plasma neopterin and high sensitivity C-reactive protein (hsCRP) levels and circadian rhythm of blood pressure in hypertensive patients with obstructive sleep apnea syndrome (OSAS). A total of 367 hospitalized hypertensive patients were recruited. They were divided into three groups according to polysomnography (PSG): hypertension alone (group A, n=212), hypertension with mild OSAS (group B, n=107) and hypertension with moderate to severe OSAS (group C, n=48). Plasma neopterin and hsCRP concentrations were measured on or after the day of PSG, and ambulatory blood pressure (ABPM) was monitored in the first week of admission. Plasma neopterin and hsCRP levels were significantly higher in group B and C compared to group A (P<0.05). Incidence of non-dippers was significantly lower in group A (44.5%) compared to group B (67.7%) and C (84.2%) (P<0.05). Nocturnal and diurnal blood pressures were negatively correlated with plasma neopterin and hsCRP. Multiple stepwise regression analysis showed that apnea hypopnea index (AHI), drop rate of systolic blood pressure, mean oxygen saturation (MSaO2), minimum oxygen saturation (SaO2 min) were the main factors for neopterin levels while AHI and MSaO2 were the major factors affecting hsCRP levels. Plasma neopterin and hsCRP levels are increased in hypertensive patients with OSAS and positively correlated with severity of OSAS.

Neopterin, a Marker of Interferon-Gamma-Inducible Inflammation, Correlates with Pyridoxal-5′-Phosphate, Waist Circumference, HDL-Cholesterol, Insulin Resistance and Mortality Risk in Adult Boston Community Dwellers of Puerto Rican Origin

Interferon-gamma (IFNG), a pro-inflammatory cytokine, increases concentrations of neopterin, a stable pteridine derivative, due to IFNG-induced transcriptional activation of the rate-limiting enzyme of pteridines biosynthesis. Neopterin concentrations were reported to correlate with metabolic syndrome (MetS), the cause of increased mortality risk, in subjects of European ancestry. We were interested to assessed neopterin correlations with clinical markers of MetS and mortality risk in population with a different genetic background, i.e., Puerto Ricans residents of Boston. Since inflammation is associated with pyridoxal-5'-phosphate (PLP) deficiency, we assessed correlations of neopterin with PLP. Plasma neopterin concentrations were evaluated in 592 adult (45-75 years of age) participants of Boston Puerto Rican Health Study. Neopterin concentrations correlated with abdominal obesity (waist circumference, r = 0.085, p < 0.038), HDL cholesterol (r = -0.15, p < 0.0001), insulin resistance (HOMA-IR, r = 0.08, P < 0.03), and plasma pyridoxal-5'-phosphate (PLP (r = -0.13, P = 0.002). Neopterin concentrations of >16 nmol/L at baseline were associated with the increased risk of mortality in 113 subjects followed for 6 years. The present results together with previously reported data in European subjects suggest a similar pattern of neopterin correlations with MetS and mortality risk in population with different genetic backgrounds. PLP is a cofactor of IFNG-induced key enzymes of tryptophan-kynurenine metabolism. Since PLP deficiency is associated with the increased production of diabetogenic kynurenine derivative, xanthurenic acid, our results suggest that up-regulated IFNG production might contribute to the development of insulin resistance. Assessment of neopterin concentrations might help to monitor the activity of IFNG-inducible inflammation associated with aging-associated medical and psychiatric disorders.

Neopterin and biopterin as biomarkers of immune system activation associated with castration in piglets1

Recent reports have shown that stressful situations may affect the production of unconjugated pterins (neopterin and biopterin). The aim of the study was to investigate the effect of castration on neopterin and biopterin plasma concentrations in piglets, using 2 groups of 12 piglets allocated to castrated and uncastrated (control) groups. Pterin concentrations were determined by HPLC with fluorescence detection. Blood samples were also analzyed for leukocyte profiles and plasma cortisol concentrations. A time × treatment interaction (P < 0.05) was detected for neopterin concentrations, such that neopterin was greater (P < 0.01) at 1 h after surgery in castrated piglets compared with precastration concentrations, and neopterin was greater (P = 0.05) in castrated than in control piglets at 1 h. Castration had no effect on biopterin concentration (P > 0.1). Time effects (P < 0.05) for neutrophil and lymphocyte concentrations and neutrophil-to-lymphocyte ratios were found. A time × treatment interaction (P < 0.01) was detected for plasma cortisol concentrations, such that cortisol was greater (P < 0.01) at 1 and 24 h after surgery in castrated piglets compared with precastration concentrations and was greater (P < 0.01) in castrated than in control piglets at 1 and 24 h. This study showed that castration activated the immune system of piglets as demonstrated by an increase in plasma neopterin concentrations.

Impact of body mass index on seminal oxidative stress

Male obesity has been linked with a reduction in sperm concentration and motility, an increase in sperm DNA damage and changes in reproductive hormones. Recent large observational studies have linked male obesity with a reduced chance of becoming a father. One of the potential underlying pathological mechanisms behind diminished reproductive performance in obese men is sperm oxidative stress. The primary aim of this study was to determine if sperm oxidative stress was more common in obese/overweight men. A total of 81 men had their body mass index (BMI) correlated with seminal reactive oxygen species (ROS) production (Nitro Blue Tetrazolium assay), sperm DNA damage (TUNEL), markers of semen inflammation (CD45, seminal plasma PMN elastase and neopterin concentration) and routine sperm parameters, together with reproductive hormones. The principal finding from this study was that oxidative stress did increase with an increase in BMI, primarily due to an increase in seminal macrophage activation. However, the magnitude of this increase was small and only of minor clinical significance as there was no associated decline in sperm DNA integrity or sperm motility with increasing ROS production. Increased BMI was also found to be significantly linked with a fall in sperm concentration and serum testosterone, and an increase in serum oestradiol.