Mean Serum Neopterin Levels Research Articles

Estimation of serum neopterin in patients with acute coronary syndrome

The aim of our study was to determine neopterin levels in patients with acute coronary syndrome, in which the release of various cytokines activates the cellular immune system. There is an increase in the number and activity of T-cells in unstable atherosclerotic plaques, and of type 1 helper T-cells that produce interferon γ, which in turn produces neopterin, a byproduct of the guanosine triphosphate-biopterin pathway and a marker for activated macrophages. We studied 600 subjects consisting of healthy volunteers and patients with noncardiac chest pain, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina. Neopterin levels were determined by high-performance liquid chromatography. Mean serum neopterin levels in ST-segment elevation myocardial infarction (11.5 ± 3.2 nmol·L(-1)), non-ST-segment elevation myocardial infarction (9.8 ± 2.9 nmol·L(-1)), and unstable angina patients (9.4 ± 2.3 nmol·L(-1)) were significantly higher than those in noncardiac chest pain patients (7.4 ± 1.9 nmol·L(-1)) and healthy volunteers (7.2 ± 0.6 nmol·L(-1); p < 0.001). These findings suggest that serum neopterin levels may be a useful marker of systemic inflammation, and measurement of serum neopterin may be helpful in assessing the risk of developing coronary heart disease.

Relationship between serum neopterin levels and coronary heart disease

The relationship between serum neopterin levels and coronary heart disease (CHD) was investigated. Eighty-six CHD patients were divided into an acute myocardial infarction (AMI) group (N = 21), an unstable angina pectoris (UAP) group (N = 35), and a stable angina pectoris (SAP) group (N = 30), based on coronary angiography (CAG), 30 subjects without CHD served as the control group. Serum neopterin levels were determined by enzyme linked immunosorbent assay (ELISA), and relationships between neopterin and the severity of stenosis, stenosis number, and the stability of coronary artery were analyzed. Serum neopterin levels were higher in the AMI and UAP groups than in the SAP and control groups (P < 0.01), but no significant differences were observed between the AMI and UAP groups or between the SAP and control groups (P > 0.05). Mean serum neopterin levels were higher in the single, double, and three vessel lesion groups than in the control group (P < 0.05), whereas there were no significant differences among the lesion groups (P > 0.05). Serum levels of neopterin were significantly higher in the type II than in the type I or type III, plaque groups (P < 0.01), the incidence of type II plaque was significantly higher in the AMI and UAP groups compared to the SAP group (P < 0.01). Neopterin likely plays a role in the occurrence and development of athermanous plaque and can serve as a useful biomarker of vulnerable plaques. Immunoreaction may be involved in the pathophysiological process of CHD.

Pravastatin therapy fails to suppress post-PCI inflammatory response measured by serum neopterin and CRP levels

Percutaneous coronary intervention (PCI) is known to induce both local and systemic inflammatory states. In addition to lowering lipid levels, statins exert well-proven anti-inflammatory effects. We investigated the effects of pravastatin on serum C-reactive protein (CRP) and neopterin levels in the short term after elective PCI. In this randomized prospective study, 93 patients undergoing elective PCI were enrolled. Group 1 (n=30) received pravastatin at a dose of 10 mg/day, Group 2 (n=29) was given 40 mg/day, and Group 3 (n=34) served as the control group and received no lipid-lowering drugs. Blood samples were drawn before and after PCI to measure serum CRP and neopterin levels. Differences among the groups for continuous variables were evaluated by the ANOVA and the Kruskal-Wallis test as appropriate. The Chi-square test was used for comparison of categorical variables. Demographic features and the characteristics of the PCI, including the number of vessels and lesions and the duration and number of inflations, did not differ among groups (p>0.05). Serum CRP and neopterin levels were significantly increased after PCI (p<0.001). Mean serum neopterin levels before and after the PCI were as follows: Group 1: 13.3±5.9 vs 22.8±15.4 nmol/L, Group 2: 16.9±10.2 vs 22.0±14.9 nmol/L, controls: 15.2±11.9 and 18.8±11.5 nmol/L. Prior pravastatin therapy had no significant effect on these inflammatory markers (F=0.5, p=0.6). Percutaneous coronary intervention induces a pronounced inflammatory response. The pre-procedural administration of 2 different doses of pravastatin seems not enough to suppress this inflammation at the short-term follow-up. Further trials are needed to clarify this issue.

Serum neopterin is elevated in patients infected with Shigella

BackgroundNeopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.MethodsIn this study, the level of neopterin was determined in serum samples obtained from patients infected with Shigella (all four species) and healthy individuals. The study population comprised of 14 patients infected with Shigella and 14 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay (ELISA).ResultsThe mean of serum neopterin concentration was 36.32 ± 9.71 nmol/L among patients infected with Shigella and 2.88 ± 0.77 nmol/L in the control group. The mean serum neopterin levels were significantly higher in the test group as compared to the normal group (p = 0.002).ConclusionThis study revealed that neopterin was elevated in patients infected with Shigella.

Serum neopterin levels in patients with non‐alcoholic steatohepatitis

Neopterin is a marker of cell-mediated immunity. It also has a fundamental role in host-defense reactions, including interactions with reactive oxygen intermediates and the promotion of local and systemic oxidative stress. The present study aimed to assess the importance of serum neopterin levels in patients with non-alcoholic steatohepatitis (NASH). Thirty-nine patients with NASH diagnosed by liver biopsy and 32 healthy adults (controls) were enrolled in the study. Serum neopterin levels were measured with an enzyme-linked immunosorbent assay in addition to other biochemical parameters, including liver enzymes. Histopathological examinations were graded as suggested by both the necroinflammatory activity grading system and the NASH scoring system. The mean serum neopterin levels were higher in patients with NASH compared to the controls (24.1 +/- 16.4 vs 16.2 +/- 9.5, P = 0.019). The histological examination of liver biopsies revealed that 34 of the patients with NASH had grade 1 steatohepatitis and only five patients had grade 2 steatohepatitis. A higher serum mean neopterin level was detected in grade 2 patients compared to grade 1 (40.6 +/- 5.6 vs 21.7 +/- 16.1, P = 0.014). A gradual increase was also observed in serum neopterin levels with the increase of the NASH score. The serum neopterin levels were significantly higher in patients with NASH compared to the controls, and levels showed an association with the severity of liver damage.

Comparison of Neopterin Levels in Patients with Coronary Artery Ectasia Versus Patients with Obstructive Coronary Artery Disease

Inflammation has been reported as an important component of vascular aneurysm formation, as found in obstructive vascular disorder. Neopterin is produced by activated macrophages and is thought to represent a marker of immune activation and macrophage activity. The plasma neopterin levels were investigated in coronary artery ectasia (CAE) patients to investigate the role of inflammation. The study population consisted of three groups: the first consisted of 28 patients with isolated CAE without stenotic lesion; the second of 27 patients with obstructive coronary artery disease (O-CAD) without CAE; and the third group of 15 control subjects with normal coronary arteries (NCA). Plasma soluble neopterin levels were measured in all patients and control subjects using commercially available enzyme-linked immunosorbent assay kits. Plasma neopterin levels were found to be significantly higher in patients with isolated CAE compared with control subjects with angiographically NCA (18.5 +/- 8.8 versus 8.7 +/- 2.6 nmol/L, respectively, P = 0.006). Although neopterin levels were higher in patients with CAE than in patients with O-CAD, they did not reach the statistically significant levels (18.5 +/- 8.8 versus 16.8 +/- 8.2 nmol/L, respectively, P = 0.77). Patients with O-CAD had significantly higher levels of neopterin compared with subjects with angiographically NCA (16.8 +/- 8.2 versus 8.7 +/- 2.6 nmol/L, respectively, P = 0.03). The mean serum neopterin levels in patients with single-vessel, two-vessel, and diffuse ectasia were as follows: 17.4 +/- 9.9 nmol/L, 19.5 +/- 8.9 nmol/L, and 20 +/- 5.5 nmol/L, respectively (P = 0.4). Patients with isolated CAE have raised levels of neopterin compared with patients with NCA, showing the possible role of inflammatory processes (monocyte/macrophage activity) in the higher levels of neopterin in patients with O-CAD.

Serum neopterin, nitric oxide, inducible nitric oxide synthase and tumor necrosis factor-α levels in patients with ischemic heart disease

Atherosclerosis, a chronic inflammatory disease, underlies the pathogenesis of coronary artery disease. The present study assessed the diagnostic possibilities of inflammatory biomarkers, serum neopterin, nitrite/nitrate (NO2(-)/NO3(-)), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), and their correlation with risk factors in patients with acute coronary syndromes and stable angina pectoris. We studied 44 patients with chronic stable angina pectoris, 46 with unstable angina, 55 with acute ST-elevation myocardial infarction and 39 age-matched healthy volunteers (control group). Serum neopterin, iNOS and TNF-alpha were determined with commercially available enzyme linked immunosorbent assay methods and NO2(-)/NO3(-) by the modified cadmium-reduction method. Mean serum neopterin levels were significantly higher in patients with unstable and stable angina pectoris in comparison to control subjects (p<0.01 and p<0.05, respectively). Serum NO2(-)/NO3(-) values were significantly elevated (p<0.01) only in patients with unstable angina. ST-elevation myocardial infarction patients with cardiac death during follow-up showed significantly lower baseline neopterin values (p<0.001), and higher NO2(-)/NO3(-) levels (p<0.05) in comparison to those without adverse events. Significantly higher NO2(-)/NO3(-) values (p<0.05) were also found in patients who had myocardial reinfarction. Serum iNOS and TNF-alpha in all patient groups were within control ranges. A strong correlation was found between neopterin and both smoking (p<0.01) and triglycerides (p<0.05) in unstable angina patients. In stable angina patients, neopterin, iNOS and TNF-alpha significantly correlated with hypertension (p<0.01) and triglycerides (p<0.05). A significant difference in neopterin concentration was found between smokers and non-smokers (p<0.05). The results of this study suggest that in stable angina patients, if studied over time, serum neopterin or NO2(-)/NO3(-) levels may indicate future plaque instability. In ST-elevation myocardial infarction patients, neopterin and/or NO2(-)/NO3(-) levels may identify patients at long-term risk of death or recurrent acute coronary events after myocardial infarction.

Neopterin as a marker for immune system activation in coal workers' pneumoconiosis

Coal workers' pneumoconiosis (CWP) is an occupational pulmonary disease that occurs by chronic inhalation of coal dust. Coal workers' pneumoconiosis is divided into two categories depending on the extent of the disease as simple pneumoconiosis (SP) and progressive massive fibrosis (PMF). Development of CWP is associated with the activation of the immune system. Neopterin is a predictive biochemical marker of cell-mediated immune activation and elevated levels of neopterin are detected in body fluids of patients with immune-related diseases. The present study was aimed to investigate whether increased serum, urine and bronchoalveolar lavage (BAL) fluid levels of neopterin is associated with the development and/or severity of CWP. Mean serum neopterin levels in SP and PMF patients (10.72 +/- 0.98 nmol/L; 14.08 +/- 3.86 nmol/L, respectively) were significantly higher than those of control group (5.30 +/- 0.47 nmol/L) (P < 0.05). Although urinary neopterin levels were also increased in SP and PMF patients (235.17 +/- 7.40 micromol/mol creatinine; 256.05 +/- 9.43 micromol/mol creatinine, respectively) as compared with the control group (140.00 +/- 5.43 micromol/mol creatinine) (P < 0.01), they were within the normal concentration range. No significant difference was observed between serum and urinary neopterin levels of SP and PMF patients. A correlation was observed between serum and urinary neopterin levels of all subjects (r = 0.525, P < 0.01). Bronchoalveolar lavage fluid neopterin levels were significantly higher in patients with SP and PMF (22.67 +/- 2.9 nmol/L; 41.67 +/- 8.68 nmol/L, respectively) compared with control subjects (6.264 +/- 1.74 nmol/L) (P < 0.05, P < 0.01, respectively). The levels of neopterin in BAL fluid were also significantly higher in patients with PMF than in those with SP (P < 0.05). These findings indicate that elevated serum and BAL levels of neopterin may be considered as a suitable biomarker for the assessment of CWP.

Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris

Serum levels of neopterin, an immune modulator secreted by activated macrophages, are elevated in patients with acute coronary syndromes compared with stable angina patients and control subjects. In unstable angina, serum neopterin levels correlate with the presence of vulnerable coronary stenosis, multiple complex coronary lesions, and patient outcome. The present study assessed the prognostic significance of raised serum neopterin concentrations in patients with stable angina pectoris. We carried out a 1-year follow-up prospective study in 297 patients with chronic stable chest pain undergoing diagnostic coronary angiography. The primary study endpoint was the composite of non-fatal myocardial infarction, unstable angina, and cardiac death. Fifty-one patients (17.2%) had adverse coronary events during follow-up. Mean serum neopterin levels were significantly higher in patients with events compared with those without (P=0.02). On multiple regression analysis, neopterin levels (P=0.021), severity of coronary artery disease (P=0.009), and a history of previous myocardial infarction (P=0.001) were independent predictors of adverse events. Serum neopterin is an independent predictor of major adverse coronary events in patients with chronic stable angina pectoris. This marker of macrophage activation may be useful for risk stratification in patients with chronic stable angina.

Soluble IL-2R, IFN-γ and Neopterin as Immunologic Markers in Patients with Tuberculosis

Background The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-γ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-γ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Method The serum sIL-2R, IFN-γ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-γ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results 1) The serum sIL-2R and IFN-γ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis(2967±2132.8 pg/ml) than in healthy controls(4949±1242.1 pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-γ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-γ levels declined from 1071±1139.4 U/ml to 1023±1920.9 U/ml(p>0.05), 41 52.8 pg/ml to 22±23.9 pg/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from 3158±2272.6 pg/ml to 3737±2307.5 pg/ml(0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusions On the basis of this study, sIL-2R, IFN-γ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients.

To determine levels of serum interferon beta (IFNbeta) neutralizing antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS treated with Betaseron or Avonex. Controversy exists over the relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such difference. To determine the role of patient profile and test methodology in IFNbeta, NAb levels need to be measured blindly and simultaneously in a predefined closely matched MS patient cohort. Serum NAb and neopterin levels were measured in closely matched patients on Avonex (n = 98) or Betaseron (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by Covance Laboratories using a competitive binding radioimmunoassay. More patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p = 0.008). Mean serum neopterin levels were lower in patients with high as compared to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found comparing the total Betaseron group to the Avonex group; however, in the subset of patients with low NAb titers, mean neopterin levels were higher in the Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling of patients on Avonex showed a decrease in neopterin levels over time between weekly doses. NAb are more commonly found with Betaseron than Avonex. More studies are needed to determine the correlation among serum neopterin levels, other biologic response markers, NAb, and disease activity in patients with MS being treated with IFNbeta.

Serum Neopterin Assay to Interpret the Main Cause of Chronic Liver Damage Involved with Plural Etiological Factors

Summary Identification of the main cause of chronic liver damage (CLD) involved with plural etiological factors is important for the management and the treatment of patients. To evaluate its clinical usefulness in interpreting the main cause of CLD involved with hepatitis C virus, alcoholic overdrinking, or fatty steatosis, which are the most frequent and troublesome etiological facotors in the daily outclinic, serum neopterin level was measured in ten healthy subjects, ten chronic hepatitis C (CH-C) patients, nine alcohol-induced liver damge (AL) patients, eight non-alcholic fatty liver (FL) patients, eight CH-C with AL padtients, seven CH-C with FL patients and ten non-B non-C chronic hepatitis (CH-NBNC) patients by using radioimmunoaasay. There were no significant difierences in the mean serum neopterin levels among the healthy subjects, the AL patients and the FL patients. The serum neopterin level in the CH-C with AL or FL patients was significantly higher than that in the AL or the FL patients and just as high as that in the CH-C patients. Furthermore, serum neopterin level in CH-NBNC patients was as high as that in the patients with CH-C. Therefore, the serum neopterin assay can easily assume the main cause of CLD involved with plural causes, so it will be very useful in the daily clinical practice as an easyto- use auxiliary test.

Neopterin as parameter of cell-mediated immunity response in thermally injured patients

Serum neopterin levels have been determined retrospectively in 22 patients with burn injuries. Neopterin, which is produced by monocytes/macrophages following stimulation by interferons, is regarded as a marker for the activation of the cellular immune response. In most patients neopterin levels were initially in the normal range. All patients had their first operation and skin tranplantation during the first week; mean neopterin levels increased significantly thereafter. Further skin transplantations or infections did not significantly influence the elevated neopterin level. This result may be due to continuous stimulation of the cellular immune system, as indicated by the elevated neopterin levels during most of the follow-up. In four low risk patients, neopterin levels always remained in the normal range. Two patients with inhalation trauma showed highly elevated neopterin levels (30–70 nmol/l) already upon admission and for 3 days thereafter. No correlation of neopterin levels with the burned body surface area was observed. However, mean serum neopterin levels were higher in the group of non-survivors (five patients) compared to survivors during the first 2 weeks after the trauma; rising neopterin levels were observed during the last 5 days before death. Although elevated neopterin levels could not be attributed either to the burn itself or to later events, the cellular immune system of burned patients was shown to be highly activated.

Serum Neopterin Levels Following Intravenous Endotoxin Administration to Normal Humans

Endotoxin was administered intravenously to five normal subjects.Measurement of serum neopterin levels demonstrated no significant change from baseline during the first 6 h after endotoxin administration, but were elevated two to four-fold at 24 h.In the three subjects in whom it was measured, a two-fold rise of the mean serum neopterin levels persisted at 48 h.The acute inflammatory events initiated by endotoxin administration to normal humans result in a delayed, but sustained, rise in serum neopterin levels which persists well after the acute phase response has subsided.