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PubMed2006

The clinical significance of serum and urinary neopterin levels in several renal diseases.

Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker associated with cell-mediated immunity in various diseases. We hypothesized that the levels of serum and urine neopterin would be elevated in renal disease, and would correlate with certain clinical parameters. We evaluated serum and urinary neopterin levels in patients with several renal diseases, including nephrotic syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with CRF and ESRD, as compared to controls. Urinary neopterin levels were also found to be elevated in patients with CRF and ESRD, as compared to controls. Serum neopterin levels showed significant positive correlation with age, serum BUN and creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, serum albumin and total iron binding capacity. Urine neopterin levels exhibited positive correlation with age and serum creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In conclusion, increased serum and urinary neopterin levels were found in some patients with renal disease and were correlated with certain clinical parameters.

Adult↗
PubMed1997

[Serum neopterin levels after extensive burns and their relationship to endotoxemia and sepsis].

The present study was performed to determine the kinetics of serum neopterin levels after major thermal injury and their relationship to endotoxemia and sepsis. This prospective study included 35 patients (32 males and three females) with total burn surface area (TBSA) greater than 30% (30%-98%), and 22 healthy volunteers who served as normal controls. The results showed that neopterin levels increased in most patients on day 3 postburn, but they were not significantly correlated with the extent of the burn surface (P > 0.05). Patients with endotoxemia had much higher neopterin values than those who showed no endotoxemia from the second week onward (P < 0.05-0.01), and circulating endotoxin and neopterin levels were positively correlated in patients who developed endotoxemia on day 14 (r = 0.368, P < 0.05) and day 21 (r = 0.439, P < 0.01) after major burns. Moreover, a high serum neopterin level was found in patients with sepsis (n = 15), and the marked elevation persisted throughout the observation period. The difference between septic and non-septic patients (n = 20) became significant on 14 and 28 days postburn. These data suggest that extensive burns can lead to an elevation of serum neopterin independent of TBSA. The endotoxin release in the circulation may be involved in the continuous formation of neopterin during the late postburn stage. In addition, the presence of a constant high neopterin level is associated with a critical event in the development of burn sepsis.

Adolescent↗
PubMed1999

Neopterin is an independent prognostic variable in females with breast cancer.

BACKGROUND: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-gamma, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in neopterin in the serum and urine of patients depends on tumor stage and type. METHODS: In a retrospective study comprising 129 females with breast cancer, urinary neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. RESULTS: Urinary neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases (P <0.05) and by tumor differentiation (P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases (P <0.001), neopterin (P <0.001), tumor size (P = 0.001), and lymph node status (P <0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases (P <0. 001), neopterin (P <0.01), and lymph node status (P <0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased neopterin concentrations was 2.5 compared with patients with neopterin concentrations within the reference interval. CONCLUSION: Urinary neopterin provides additional prognostic information in patients with breast cancer.

Adult↗
PubMed2001

[Changes in serum neopterin levels in patients after trauma].

OBJECTIVE: To evaluate the clinical significance of changes in serum neopterin levels in patients after trauma. METHODS: 41 patients with mechanical injury were divided into three groups according to the injury severity score (ISS). In all patients, blood collection was started within 24 h after injury, and blood samples were obtained at 3, 7, 14, and 21 d post-trauma. The relationship was determined between serum neopterin levels and ISS, multiple organ dysfunction syndrome (MODS) and prognosis in patients. RESULTS: Patients with ISS > or = 25 showed a high neopterin level compared with those with ISS < 16 (P < 0.05 or P < 0.01), and a correlation between mean neopterin levels and ISS was observed in severely injured patients (r = 0.518, P < 0.05). High neopterin levels were measured in patients who developed MODS, showing a persistent marked elevation from day 3 post-trauma onward. The difference between MODS and non-MODS patients was significant on days 3, 7, and 14 after acute insults (P < 0.05 or P < 0.01). In addition, serum neopterin levels of patients with fatal outcome were much higher than those of surviving patients, and it exceeded 50.0 nmol/L in most cases prior to termination (8/12 cases, 66.7%). CONCLUSIONS: Mechanical injury can cause a constant increase in neopterin level, implying an intact reaction by T lymphocytes and macrophage axis. The measurement of serum neopterin might serve as a tool for the evaluation of injury severity, early detection of MODS as well as prediction of outcome in patients after trauma.

Adult↗
PubMed2001

[The predictive value of serum neopterin for multiple organ dysfunction syndrome in extensively burned patients].

OBJECTIVE: To evaluate the predictive value of serum neopterin for multiple organ dysfunction syndrome (MODS) in extensively burned patients. METHODS: Twenty-nine burn patients with TBSA of more than 70% were included in this study, and these patients were divided into two groups according to the occurrence of MODS. Blood samples were obtained on 1, 3, 7, 14, 21 and 28 postburn days (PBDs). And serum neopterin levels were determined by radioimmunossay. To evaluate the predictive power of neopterin, sensitivity, specificity, predictive value of a positive/negative test were calculated for the diagnosis of MODS. RESULTS: Serum neopterin levels in MODS group were significantly higher than those in non-MODS group on 3, 7, 14 and 21 PBDs (P < 0.05 similar 0.01). And a positive correlation was found between neopterin levels and MODS scores in patients who developed MODS on 3, 7 and 21 PBDs (r = 0.470 similar 0.811). In a period of up to 28 PBDs, neopterin levels exceeding 35.0 nmol/L were associated with MODS by a clinical sensitivity of 81.1%, a specificity of 89.9%, a positive predictive value of 81.1%, and a negative predictive value of 89.9%. CONCLUSION: These data indicated that the presence of constant high neopterin serum levels appear to be associated with the development of postburn MODS. Serum levels of neopterin might be a useful marker for the early identification of extensive burned patients at risk for MODS.

Adolescent↗
PubMed2005

[Neopterin: a marker used for monitoring infections].

Neopterin released by monocytes/macrophages upon activation by interferon-gamma secreted from T-lymphocytes, is a sensitive indicator of cell-mediated immune activation. Chemically, neopterin is a pyrazino-pyrimidine derivative, namely, 2-amino-4 hydroxy-(1',2',3' trihydroxypropyl)-pteridine. Biosynthetically, neopterin derives from guanosine triphosphate (GTP), and is a biologically stable cytokine. Increased concentrations of neopterin in serum and urine have been found in various infections (especially viral), autoimmune diseases, malignant disorders, and during allograft rejection episodes. In addition, there is a close relationship between high neopterin levels and systemic inflammatory diseases, septicemia and surgical stress. Measurement of neopterin concentration in human body fluids such as serum, urine, cerebrospinal fluid and pleural fluid, allows insight into a cell-mediated immune response. In recent years neopterin becomes an important laboratory parameter for clinical and therapeutical follow-up of diseases involving the cellular immune system. In this review article, the clinical use of neopterin as a marker in the diagnosis and monitorization of the infectious diseases has been discussed.

Biomarkers↗
PubMed2005

The diagnostic values of serum, pleural fluid and urine neopterin measurements in tuberculous pleurisy.

SETTING: Pulmonary department of a medical academy in Ankara, Turkey. OBJECTIVE: Neopterin is a marker of cell-mediated immunity, and it has been demonstrated that neopterin levels of various body fluids could be elevated in tuberculosis. We aimed to investigate diagnostic values of serum, pleural fluid and urine neopterin measurements in tuberculous pleurisy (TP). DESIGN: Serum, pleural fluid and urine neopterin levels were measured in 34 patients with TP and in 29 patients with pleural effusion of non-tuberculous origin as controls. RESULTS: Neopterin levels in serum, pleural fluid and urine (38.28 +/- 14.18 nmol/l, 38.97 +/- 14.18 nmol/l and 759.15 +/- 622.74 micromol/mol, respectively) were significantly higher in patients with TP than those with non-tuberculous pleural effusion (22.57 +/- 6.02 nmol/l, 21.88 +/- 6.90 nmol/l and 343.10 +/- 233.65 micromol/mol, respectively). Pleural fluid neopterin > or =30 mol/l gave the best diagnostic yield, with 85% sensitivity, 93% specificity, 94% positive predictive value, 84% negative predictive value and 89% diagnostic accuracy, although it is not superior to pleural fluid adenosine deaminase determination. CONCLUSION: We have suggested that elevated serum, pleural fluid and urinary neopterin levels in TP with respect to pleural effusions of non-tuberculous origin may reflect activation of cell-mediated immunity and that pleural fluid neopterin measurement may be of value in the differential diagnosis of TP.

Adolescent↗
PubMed2005

Evaluation of a new enzyme-linked immunosorbent assay for the determination of neopterin.

BACKGROUND: Determination of neopterin especially evaluated for use on the Behring ELISA Processor BEP III highly suited for the demands of blood donation screening in blood banks. METHODS: A new commercially available enzyme-linked immunosorbent assay (ELISA) was developed for the detection of neopterin, a low-molecular-mass pteridine. Neopterin is produced by interferon-activated macrophages or monocytes during the activation of the cellular immune system in various diseases. In Austria testing of neopterin to detect cellular immune activation is mandatory since 1995. The former assay version has been used for the measurement of neopterin at the Medical University Graz. As a result of the cooperation with the blood bank in Graz and the Dade Behring company we have developed a new ELISA kit based on a special coating procedure. For comparison we performed measurements with the current IBL Neopterin ELISA version, the HPLC method and with the ELItest Neopterin ELISA (BRAHMS). The new assay is based on a simple assay procedure with two incubations of 1 h and of 30 minutes. RESULTS: Linear regression analysis showed a significant correlation to the HPLC method. The assay is accurate and precise. CONCLUSIONS: The above mentioned neopterin assay as an alternative method to other ELISA kits and the HPLC is highly suited for automation and was especially evaluated as a simple, rapid and reproducible version for the Behring ELISA Processor BEP III during this study.

Blood Donors↗
PubMed1991

Plasma neopterin as an adjunct to C-reactive protein in assessment of infection.

C-reactive protein (CRP) concentrations are increased in plasma in people with inflammatory conditions and bacterial infections. Plasma neopterin concentrations are increased in people with bacterial septicemias, viral infections, and graft vs host disease. Plasma concentrations of CRP and neopterin were measured daily in 21 bone-marrow transplant (BMT) patients, 64 patients in intensive-care units (ICU), and 12 patients with squamous cell carcinoma of the head and neck (HN). In the BMT patients, plasma neopterin measurements in addition to CRP measurements allowed infectious episodes to be distinguished from graft vs host disease. In the ICU patients, increased concentrations of CRP were not specific for infection and the additional plasma neopterin measurements did not improve this specificity. In all three patient groups, the derivation of a neopterin/CRP ratio was of no clinical use. These three groups of patients showed patterns of CRP and neopterin concentrations characteristic of their underlying diseases, the BMT patients with the immunological activation of graft vs host disease showed predominantly increased concentrations of plasma neopterin, ICU patients with infectious and inflammatory conditions had increased concentrations of both CRP and neopterin in plasma, and the HN group with localized inflammation showed increased plasma concentrations of CRP without increases in neopterin.

Adolescent↗
PubMed1991

Urinary neopterin in patients with systemic lupus erythematosus.

Concentrations of neopterin were measured in urine specimens from 35 patients with active and eight with inactive systemic lupus erythematosus (SLE). Compared with those of apparently healthy controls, neopterin concentrations were higher in patients with active disease (P less than 0.001) and with inactive disease (P less than 0.01), those in patients with active disease being significantly higher than those in patients with inactive disease (P less than 0.001). The correlation between the neopterin concentration and evidence of disease activity was good. All of the patients with clinically active SLE had increased neopterin, but for only 37.5% (three of eight) did the neopterin concentration exceed the upper normal limit during clinical remission. The increase in neopterin concentration did not correlate with clinical courses or severity of renal function. Moreover, serial determinations of neopterin in active SLE patients showed a rapid decrease of initially high concentration, paralleling a decline of clinical activity after initiation of medical therapy. Thus, urinary neopterin may be a useful marker for monitoring disease activity in SLE patients.

Adolescent↗
PubMed1987

Clinical significance of neopterin for prognosis and follow-up in ovarian cancer.

Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. The prognostic value of pretherapeutically and of serially measured urinary neopterin levels in patients with ovarian cancer was assessed, in a blinded manner, by analysis of 658 urine specimens from 74 women. The specimens were collected during a 5-year period (January 1981 to January 1986). Thirty-one deaths due to cancer were observed during the study period. By statistical analysis, a significant predictive value of pretherapeutic neopterin levels was found and compared with that of other possible prognostic clinical and laboratory findings. Multivariate analysis, using stratification by tumor stage, demonstrated that this predictive information was independent of other variables. A significant association was found between serial neopterin measurements and the current risk of death during follow-up (P less than 0.0001). In addition, current death risk was correlated with neopterin levels measured 6 months previously (P = 0.026). The histological outcome at surgical reexamination was correlated with the current neopterin levels (P = 0.016). Further, normal neopterin levels in women with evidence of tumor at surgical reexamination were shown to be a sign of better prognosis than elevated levels. Measurement of urinary neopterin levels during follow-up of women with ovarian cancer appears to be a valuable adjunct to conventional techniques, particularly in patients refusing explorative surgery.

Biopterins↗
PubMed1987

Determination of neopterin in serum and urine.

Concentrations of neopterin, a product of activated macrophages, in serum from 662 apparently healthy individuals (ages 1 to 97 years, median 22 years) were measured by radioimmunoassay and the results statistically analyzed. Consistent with prior investigations on the urinary excretion of neopterin, we found no significant sex dependence, but values for subjects younger than 18 or older than 75 years were significantly higher. Renal clearance of neopterin in nine healthy individuals was 218 (SD 44) mL/min, which suggests that the kidneys have an active role in neopterin excretion. Results for neopterin concentrations measured in serum by RIA and "high-performance" liquid chromatography (HPLC) are consistent, but for urinary neopterin the concordance between methods was weak. Therefore, the RIA should be used only for measuring neopterin in serum. In comparison of the clinical utility of serum neopterin and urinary neopterin/creatinine concentrations, in patients with gynecological tumors, the latter values (measured by HPLC) discriminated slightly better between patients with favorable and unfavorable prognoses.

Adolescent↗
PubMed1986

Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix.

In vitro, neopterin, a pyrazinopyrimidine compound, is excreted by human monocytes-macrophages after induction by supernatants from activated T-lymphocytes or by recombinant gamma-interferon. In vivo, it represents a noninvasive test for activation of cellular immune reactions. To evaluate the prognostic value of pretherapeutic urinary neopterin levels and of serial neopterin measurements during follow-up in women with cervical cancer, 1088 urine specimens from 186 consecutive patients were analyzed. Clinical assessments were made without knowledge of the results of neopterin assays (a "blinded" assessment). During the observation period (June 1980 to March 1984), 27 relapses, 18 metastases, and 26 deaths were seen. The prognostic significance of pretherapeutic neopterin and other possible prognostic clinical and laboratory parameters was tested by the univariate and multivariate Cox proportional hazards model using a stratification according to stage and surgical treatment. The combination of age at diagnosis, pretherapeutical hemoglobin, leukocyte count, and neopterin was found to predict survival best. On the basis of this result, risk groups were identified exhibiting markedly different survival behavior. A highly significant association was found between serial neopterin measurements and the risk for a relapse, metastasis, or death. The data suggest that urinary neopterin levels might be a useful adjuvant parameter in monitoring women with cervical cancer.

Adenocarcinoma↗
PubMed1984

Urinary neopterin in the diagnosis and follow-up of neoplasia: a biochemical parameter to detect cell-mediated immune response.

Neopterin is excreted at high levels during disease states challenging the T-lymphocyte-macrophage system. Stimulation of T-lymphocytes in mixed lymphocyte culture in the presence of macrophages is accompanied by raised neopterin levels in the supernatant. Neopterin may therefore be considered a specific indicator of cell-mediated immunity. Pretreatment analysis of patients with hemopoietic (191), urological (82) and gynecological (224) neoplasia revealed neopterin levels above the upper normal limits, with frequencies ranging from 57% (cervical carcinoma) to 96% (chronic lymphocytic leukemia). In patients with tumors of the genitourinary tract or with hemopoietic neoplasms, urinary neopterin levels were correlated with the tumor burden and became normal when remission was achieved. In gynecological cancer long term follow-up studies showed the value of neopterin excretion levels as a tumor marker. Tumor progression was indicated early by a rising neopterin level. Based on a comparison of different tumor types, the association of cell-mediated immunity and of neopterin excretion levels in less differentiated neoplasm is discussed.

Adolescent↗
PubMedDate not supplied

A study of interactions among markers of macrophage functions in metastatic solid tumors: neopterin levels in relation to those of tumor necrosis factor-alpha and of soluble interleukin-2 receptors.

High levels of the macrophage activation marker neopterin have been described in metastatic cancer patients. Since macrophages may either counteract or stimulate tumor development, it is important to establish which macrophage activity is mainly related to neopterin release. The present study was carried out to evaluate neopterin levels in metastatic solid tumor patients in respect with the antitumor macrophage cytokine TNF and with soluble IL-2 receptor (SIL-2R), whose secretion is stimulated by macrophages and it is associated with the immunosuppressive status of cancer patients. The study included 35 patients with metastatic solid neoplasms. Serum levels of neopterin, TNF and SIL-2R were measured in blood samples collected during the morning. Abnormally high concentrations of neopterin were seen in 18/35 (51%) patients. Patients with high levels of neopterin showed significantly higher concentrations of SIL-2R than those with normal neopterin values, whereas no difference was found in TNF levels. This study would suggest that the increased secretion of neopterin may reflect macrophage-mediated immunosuppression in metastatic solid neoplasms, rather than to be associated with the antitumor activity of macrophages.

Adult↗
PubMed1997

Neopterin as a marker for cell-mediated immunity in patients with pulmonary tuberculosis.

SETTING: Cell-mediated immunity (CMI) involves macrophage activation and T cell proliferation. These two parameters are compared in this study. OBJECTIVE: To ascertain the role of neopterin as a biochemical marker for CMI in patients with pulmonary tuberculosis. DESIGN: We measured neopterin levels in serum and the culture supernatants of peripheral blood mononuclear cells (MNC) after stimulation with purified protein derivative (PPD) in 11 patients with pulmonary tuberculosis and 10 healthy individuals. Lymphocyte proliferative response to PPD was carried out in these two groups. RESULTS: The mean concentration of serum neopterin was significantly higher in patients than in controls (P < 0.01). The spontaneous release of neopterin was significantly higher in culture supernatants of MNC from patients when compared with those of healthy controls (P < 0.05). Release of neopterin from MNC stimulated with PPD, however, was similar in both groups. The neopterin release and the stimulation index (SI) in lymphocyte proliferation assay were not comparable, suggesting that these two parameters do not run in parallel for measuring the status of CMI. However, serum concentration of neopterin was inversely related to the SI in a large proportion of subjects (66%). CONCLUSION: Measurement of neopterin, a soluble product of immune cells (macrophage), may provide information on the state of CMI.

Adult↗
PubMedDate not supplied

Urinary neopterin levels in acute viral hepatitis.

Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterin levels were related to the clinical activity of the viral disease. In patients with nonviral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.

Acute Disease↗
PubMed2000

Oxidation of 7,8-dihydroneopterin by hypochlorous acid yields neopterin.

In vitro, interferon-gamma stimulates primate monocytes/macrophages to produce the pteridines neopterin and 7,8-dihydroneopterin. These pteridines are capable of modulating the oxidative potential of reactive species. Neopterin is pro-oxidative whereas 7, 8-dihydroneopterin is an effective antioxidant. In the presence of oxygen, 7,8-dihydroneopterin is rapidly oxidized and after loosing the side chain 7,8-dihydroxanthopterin is formed. It is considered that under physiological conditions, 7,8-dihydroneopterin cannot be a source for neopterin production. In this study it is demonstrated that hypochlorous acid is capable to oxidize 7,8-dihydroneopterin yielding neopterin. Neopterin is less affected by hypochlorous acid, and in a mixture of both pteridines similar to the in vivo situation, only 7,8-dihydroneopterin is oxidized, thereby increasing the ratio towards neopterin. The findings may beat relevance for the in vivo situation since hypochlorous acid shifts the neopterin/7, 8-dihydroneopterin ratio towards the side of neopterin, hence probably increasing the oxidative potential in a micro-environment.

Chromatography, High Pressure Liquid↗