Plasma Neopterin Research Articles

Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease. Methods: Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry. Results: Plasma neopterin levels were significantly higher in TC patients compared with SAP patients ( P <0.0001) or UAP patients ( P <0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P<0.05) and serum C-reactive protein levels (R=0.38, P<0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC. Conclusions: This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.

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.

Comparative Study of Blood Neopterin and Biopterins in Patients with COVID-19 and Secondary Bacterial Infection.

Background/Objectives: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. Methods: Fifty-two patients with COVID-19 admitted to two tertiary care centers were included. They were divided into a severe group (intubated + mechanical ventilation) (n = 10) and a moderate group (non-intubated + oxygen administration) (n = 42), and changes over time in plasma NP, plasma BPs, IFN-γ, lymphocyte count, CRP, and IL-6 were investigated. Four of the patients in the severe group (n = 10) developed secondary bacterial infections during treatment. Plasma NP and plasma BPs of patients with bacterial sepsis (no viral infection) (n = 25) were also examined. Results: The plasma NP, IL-6, CRP, and SOFA levels were significantly higher in the severe group, while the IFN-γ level and lymphocyte count were significantly lower. The higher plasma NP in the severe group persisted only up to 1 week after symptom onset. The plasma BPs were higher in complications of bacterial infection. Conclusions: The timing of sample collection is important for assessing severity through plasma NP, while plasma BPs may be a useful diagnostic tool for identifying the development of secondary bacterial infection in patients with COVID-19. Further investigation is needed to clarify the mechanism by which NP and BPs, which are involved in the same biosynthetic pathway, are differentially activated depending on the type of pathogen.

Distinct Effects of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors on Soluble Biomarkers in Blood and Cerebrospinal Fluid of People With HIV.

Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immunomodulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH. Cross-sectional single-center (United States) analysis in 184 PWH on ART with plasma HIV RNA < 200 copies/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and clinical conditions. Participants were mostly middle-aged men, with median CD4+ T cells of 620/µL. In adjusted models, SSRI use was associated with 3 PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=.14, P = .040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=-.12, P = .042); and higher plasma sCD14 with lower sCD40L (aβ=.15, P = .042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=.22, P = .004). Statins and ACEIs showed no association. SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation, and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.

Assessment of The Level of Neopterin in Oral Fluid and Blood Plasma in Patients with Rheumatoid Arthritis

Assessment of The Level of Neopterin in Oral Fluid and Blood Plasma in Patients with Rheumatoid Arthritis

Inflammatory markers and neopterin levels in relation to mild COVID-19.

The immunopathology of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection involves an excessive inflammatory response. Approximately 80% of patients with coronavirus disease 2019 (COVID-19) have a mild illness, 20% require hospitalization, and approximately 5% require intensive care. Neopterin is a macrophage activation marker produced by monocytes and macrophages following activation by interferon-gamma (IFN-γ). It is crucial to determine neopterin levels and evaluate them together with inflammatory, coagulation, and biochemical markers in moderate/mild SARS-CoV-2 infection. The present study compared plasma neopterin and inflammatory as well as biochemical markers of 50 patients with COVID-19 and 38 healthy volunteers without COVID-19. The data of 38 participants did not show statistically significant differences in serum neopterin levels between the mild/moderate COVID-19 and control groups (p=0.259). White blood cell (WBC), neutrophil, lymphocyte, platelet (PLT), hemoglobin (HGB), procalcitonin (PCT), ferritin, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR) and lymphocyte CRP ratio (LCR) values were significantly different between the study groups (p<0.001, p=0.001, p=0.001, p<0.001, p=0.014, p<0.001, p=0.001, p<0.001, p=0.004, p<0.001, p<0.001, respectively). According to the ROC analysis, the WBC, PT, Na, and LCR values exceeding the cutoff values may be predictive of COVID-19. Although there were no significant differences in serum neopterin levels between the groups, there were high values in patients with severe SARS-CoV-2 infection in previous studies and these values were maintained for a long time. The present study found that neopterin levels were not elevated in mild/moderate COVID-19 patients.

High Plasma Levels of Neopterin Are Associated with Increased Mortality among Children with Severe Malaria in Benin.

Among the barriers to accessing adequate treatment and high-level monitoring for malaria febrile patients is the lack of effective prognostic markers. Neopterin, which is a marker of monocyte/macrophage activation, was found have increased during severe malaria. In this study, we used quantitative ELISA in order to assess the levels of plasma soluble neopterin in 151 patients from a cohort of Beninese children with severe malaria. We evaluated the prognostic accuracy of this molecule in order to predict the outcome of the disease. Our results show that neopterin levels were not significantly different between patients with different forms of severe malaria, including severe non-cerebral malaria (SNCM) and cerebral malaria (CM). However, the levels of this molecule were found to be higher in patients with severe malarial anemia (SMA) among both CM and SNCM cases (p-value = 0.02). Additionally, the levels of this molecule were found to be higher in patients who died from these pathologies compared to those who survived among the two clinical groups (p-value < 0.0001) and within the same group (p-value < 0.0001 for the CM group, p-value = 0.0046 for the SNCM group). The AUC-ROC for fatality among all the severe cases was 0.77 with a 95%CI of (0.69-0.85). These results suggest that plasma neopterin levels constitute a potential biomarker for predicting fatality among severe falciparum malaria patients.

Decreasing Tryptophan and Increasing Neopterin Plasma Levels During Pregnancy are Associated with High First Trimester Porphyromonas gingivalis K-Serotype IgG Serointensity in a Cohort of Hispanic Women.

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 and kynurenine would occur in pregnant women with elevated IgG antibodies to Pg capsular (K) serotypes. Venous blood of 52 Hispanic pregnant women with a mean age (SD) of 31.8 (5.9) years was sampled once per trimester of pregnancy (V1, V2, V3), and plasma was obtained and stored. ELISAs were used to measure Pg capsular (K) serotype IgG serointensity (V1 only) and neopterin levels (V1-V3). Tryptophan and kynurenine (V1-V3) were measured with high-performance liquid chromatography. The participants having IgG serointensity for any of the seven Pg K serotypes in the highest quartile were defined as the "High PgK_IgG" group and those having IgG serointensity for all K serotypes in the lowest three quartiles were defined as the "Low PgK_IgG" group. Statistics included multivariable linear and nonparametric methods. Significant decreases in plasma tryptophan levels and increases in neopterin during gestation were found in "High PgK_IgG" women but not in "Low PgK_IgG" women. Kynurenine changes were not significantly different between the two groups. If replicated in larger studies and further characterized clinically, radiologically, and microbiologically, our results may potentially lead to novel interventional targets, as well as the development of more complete prognostic and predictive interactive biomarkers for adverse obstetrical outcomes and peripartum depression, and their prevention.

Monocyte subsets display age-dependent alterations at fasting and undergo non-age-dependent changes following consumption of a meal

BackgroundMonocytes are a heterogenous population of immune cells whose subsets and functions become substantially dysregulated with advanced age. Although much of our current understanding of the age-related changes in monocytes is derived from fasting blood samples, most people are predominately in the postprandial state during waking hours. As hormonal, metabolic, and immunological changes in response to the consumption of a meal are manifested in postprandial blood, it’s unclear how age-dependent changes in peripheral monocytes at fasting are impacted by a dietary challenge.ObjectiveWe investigated the impact of age and meal consumption on circulating monocyte frequencies and subsets defined as classical (CD14 + CD16-), intermediate (CD14 + CD16 +), or non-classical (CD14dim CD16 +) in a cohort of 349 healthy adult volunteers grouped into categories based on their age: young adults (18–33 y, n = 123), middle adults (34–49 y, n = 115), and older adults (50–66 y, n = 111).ResultsFollowing 12-h fast total monocyte counts inversely correlated with subject age. Older adults had significantly fewer circulating monocytes along with elevated levels of TGs, cholesterol, glucose, IL-6, IL-8, TNF, neopterin, and CCL2 compared with young adults. Circulating monocyte pools in older adults consisted of smaller proportions of classical but larger proportions of intermediate and non-classical monocytes. Proportions of classical monocytes were inversely correlated with plasma TNF, IL-8, and neopterin while intermediate monocytes were positively correlated with plasma IL-6, TNF, and neopterin. Three hours after consuming a fat-containing meal postprandial monocyte counts increased in all age groups. Despite age-dependent differences in monocyte subsets at fasting, consumption of a meal induced similar changes in the proportions of classical and non-classical monocytes across age groups. Within the circulating postprandial monocyte pool, percentages of classical monocytes decreased while non-classical monocytes increased. However no change in precursory intermediate monocytes were detected. Our study confirms that ageing is associated with changes in monocyte frequencies and subsets and shows that consuming a fat-containing meal induces temporal changes in monocyte frequency and subsets independently of subject age.Clinical trialRegistered on ClincialTrials.gov (Identifier: NCT02367287)

Clinical significance of plasma-free amino acids and tryptophan metabolites in patients with non-small cell lung cancer receiving PD-1 inhibitor: a pilot cohort study for developing a prognostic multivariate model

BackgroundAmino acid metabolism is essential for tumor cell proliferation and regulation of immune cell function. However, the clinical significance of free amino acids (plasma-free amino acids (PFAAs)) and tryptophan-related metabolites...

Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy.

Chronic inflammation contributes to the pathogenesis of depression in persons with HIV (PWH). Neopterin, a biomarker of HIV-related immune activation that partially normalizes with antiretroviral therapy (ART), correlates with major depressive disorder (MDD) and subclinical depressive symptoms in persons without HIV and acutely infected, young PWH. The sensitivity of neopterin, however, to both lifetime and current depression is poorly understood in older PWH on suppressive ART. Participants were 70 PWH and 35 persons without HIV (HIV-) who were at least 50 years old and completed standardized neurobehavioral and neuromedical assessments. Depressive symptoms in the past 2 weeks, measured with the Beck Depression Inventory-II (BDI-II), and lifetime MDD diagnoses, defined as meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a depressive episode at any point in one's lifetime, were separately modeled as a function of plasma neopterin levels in the full sample and by HIV serostatus. Compared with HIV- adults, PWH had higher neopterin levels (P < 0.001) and BDI-II scores (P < 0.01) and were more likely to have lifetime MDD (P < 0.01). Higher neopterin related to lifetime MDD, but only in PWH, even after controlling for clinically relevant comorbidities and treatment factors in logistic regression (odds ratio = 3.11, P = 0.002). Higher neopterin correlated with higher BDI-II scores in the full sample (rs = 0.25; P = 0.010), but not within either group (PWH: rs = 0.03, P = 0.819; HIV-: rs = 0.09, P = 0.588). Neopterin was associated with lifetime MDD, but not current depressive symptoms in older PWH on suppressive ART. This may reflect a legacy of inflammation-related disruptions to amino acid metabolism and neurotransmitter synthesis, similar to prior observations. Identification of biopsychosocial and resilience factors underlying the null association between neopterin and current depression in older PWH is warranted.

Circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during chemoradiation in patients with cervical carcinoma

Abstract The aim of this study was to investigate the changes in circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during the course of chemoradiation in patients with cervical cancer. Sixteen patients with histologically confirmed carcinoma of the uterine cervix, aged 53 ± 15 years (range 29–76 years), were included in this study. Plasma neopterin, kynurenine, and tryptophan were determined with an enzyme-linked immunosorbent assay. Plasma citrulline was measured with high-performance liquid chromatography. Compared to baseline, citrulline concentration was markedly and statistically significantly decreased at visits 2, 3, and 4, while returning to pretreatment concentrations at visit 5. A significant increase in serum neopterin concentrations was observed at visits 4 and 5. With the exception of decreased kynurenine/tryptophan ratio at visit 3, no significant changes were observed in the concentrations of kynurenine, tryptophan, and kynurenine/tryptophan ratio throughout the course of the treatment. In conclusion, present data demonstrate that citrulline concentrations decrease early and neopterin concentrations increase late during the course of chemoradiation in patients with cervical carcinoma. Citrulline represents a biomarker of intestinal toxicity in this population.

Association of markers of vascular inflammation with blood pressure in midlife: the Hordaland Health Study

Abstract Background Hypertension is a pro-inflammatory condition. A steeper rise in blood pressure (BP) has been observed in middle-aged women than men. However, sex-specific associations of vascular inflammation with midlife BP has not been much explored. Purpose To test the association of markers of vascular inflammation, including neopterin, kynurenin:tryptophan ratio (KTR) and high sensitive C-reactive protein (CRP) with BP. Methods Circulating levels of neopterin, KTR and CRP were measured in 2042 women and 1646 men aged 47–49 years from the community-based Hordaland Health study. The associations with systolic and diastolic BP were tested in sex-specific linear regression analyses and adjusted for body mass index, serum total- and high-density lipoprotein cholesterol, triglycerides, creatinine, physical activity, daily smoking and diabetes. Results Compared to men, women had lower average BP (124/72 vs. 131/78 mmHg, p&amp;lt;0.001), higher plasma neopterin (7.5 vs 7.0 nmol/l, p&amp;lt;0.001) and comparable plasma KTR and serum CRP (both p&amp;gt;0.05). In multivariable analyses 1) higher neopterin was associated with higher diastolic BP in women, but not in men; 2) higher CRP was associated with higher systolic and diastolic BP in women, but not in men; 3) no association of higher KTR with BP was found in either sex (Table 1). A significant sex-interaction between neopterin and diastolic BP was found. Conclusion Among participants in the Hordaland Health study, higher circulating levels of neopterin and CRP with higher BP was found among women only, suggesting that vascular inflammation contributes to BP elevation in middle-aged women. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Bergen

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome.

We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10–3 versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10–8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10–3) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ2p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.

Comparison of the Levels of Neopterin, CRP, and IL-6 in Patients Infected with and without SARS-CoV-2

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers to reveal the significance of NP measurements in pathological states.Methods: Plasma NP, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 13 patients with non-COVID-19 respiratory disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently.Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while both CRP and IL-6 were not changed significantly. Among the COVID-19 patients, all three values increased with the severity of symptoms. NP levels were not correlated with CRP or IL-6 levels in COVID-19 patients but were correlated with IL-6 levels in non-COVID-19 patients. The CRP levels were correlated with those of IL-6 in both the COVID-19 and non-COVID-19 patients.Conclusions: The elevation of NP levels was distinct from those of CRP and IL-6 in COVID-19 patients. Our data suggest that NP is produced in different signaling pathways and/or cells than CRP and IL-6. Further study on the signaling pathway to induce NP is expected

Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin

ObjectivesOxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ–mediated immune...

Ecological, parasitological and individual determinants of plasma neopterin levels in a natural mandrill population.

Investigating how individuals adjust their investment into distinct components of the immune system under natural conditions necessitates to develop immune phenotyping tools that reflect the activation of specific immune components that can be measured directly in the field. Here, we examined individual variation of plasma neopterin, a biomarker of Th1 immunity in wild mandrills (Mandrillus sphinx), who are naturally exposed to a suite of parasites, including simian retroviruses and malaria agents. We analyzed a total of 201 plasma samples from 99 individuals and examined the effect of sex, age, social rank, reproductive state and disease status on neopterin levels. We found higher neopterin concentrations in males than females, but were unable to disentangle this effect from possible confounding effects of retroviral infections, which affect nearly all adult males, but hardly any females. We further detected a non-linear age effect with heightened neopterin levels in early and late life. In addition, adult males that harbored very high parasitaemia for Plasmodium gonderi also showed high neopterin levels. There was no effect of social rank in either male or female mandrills, and no effect of female reproductive state. Taken together, these results indicate that plasma neopterin may prove useful to investigate individual variation in investment into specific immune components, as well as to monitor the dynamics of immune responses to naturally occurring diseases that elicit a Th1 immune response.

Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Abstract Introduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis. Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured. Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p&lt;0.008 and p&lt;0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p&lt;0.02 and p&lt;0.0002 respectively. Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children. Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya. HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14, and neopterin were measured before ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months, and neuropsychological tests were performed at 5.8-8.2 years after initiation of ART (N = 27). The relationship between neurodevelopment and sCD163, sCD14, and neopterin at entry and 6 months after ART was assessed using Cox proportional hazards models and linear regression. Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 months; P = 0.006) and supported walking (10 vs 12 months; P = 0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 months; P = 0.006; adjusted hazard ratio, 0.47; P = 0.02), threw toys later (18 vs 17 months; P = 0.01; adjusted hazard ratio, 0.53; P = 0.04), and at median 6.8 years after ART, had worse neuropsychological test scores (adj. mean Z-score differences, cognition, -0.42; P = 0.07; short-term memory, -0.52; P = 0.08; nonverbal test performance, -0.39, P = 0.05). Before ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. After ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.

Simultaneous analysis of neopterin, kynurenine and tryptophan by amine-HPLC shows minor oxidative stress from short-term exhaustion exercise

Abstract Introduction: Neopterin, kynurenine and tryptophan can be used to measure activation of monocytes and macrophages during immunological events such as exercise inducing inflammation. Endurance exercise and high-impact sports have shown significant increases in these biomarkers. Measurement is typically conducted by high-performance liquid chromatography (HPLC) using C18 or SCX columns. However, kynurenine and tryptophan are not measured simultaneously to neopterin using these separation systems. Here we have used an amine column for separation and simultaneous determination of neopterin, kynurenine and tryptophan. Methods: Optimization and validation for the amine-HPLC method was conducted using plasma from 43 participants subjected to a short maximal exercise bicycling regime or rest period. The order of exercise and rest was randomized and separated by a 3-5 week washout period. Results: Using an amine column developed with ammonium acetate formic acid (33%) and acetonitrile (72%) provided optimal separation and run time for analysis. Neopterin increased significantly post-exercise and subsided to baseline by 30 minutes. Total neopterin remained elevated until 60 minutes following exercise. Conclusion: Amine-HPLC can be used for simultaneous determination of kynurenine, tryptophan and neopterin in plasma. Short intense exercise causes a significant increase in plasma neopterin suggesting a prolonged activation of monocytes and macrophages.