Urinary Neopterin Concentrations Research Articles

Serial Urinary Neopterin Measurements Reflect the Disease Course in Patients with Epithelial Ovarian Carcinoma Treated with Paclitaxel/Platinum Chemotherapy

Abstract Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have been reported in patients with cancer, including epithelial ovarian carcinoma (EOC). We have assessed urinary neopterin before the treatment and then daily during the therapy with paclitaxel/platinum combination in 5 EOC patients. A correlation was observed between the clinical course and serial urinary neopterin concentrations. We conclude that the determination of serial urinary neopterin concentrations may be useful for monitoring of EOC patients during chemotherapy.

Urinary Neopterin in Patients Treated with Gefitinib

Abstract Inhibitors of epidermal growth factor receptor (EGFR), including low molecular weight inhibitor erlotinib and gefitinib, have been demonstrated to be active antitumor agents in patients with non-small cell lung carcinoma and head and neck carcinomas. Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have also been reported in patients with lung carcinoma and head and neck carcinomas. EGFR blockade has been reported to induce immune activation. We have measured, using high performance liquid chromatography, urinary neopterin in patients with non-small cell lung carcinoma and head and neck carcinomas treated with gefitinib. Intestinal permeability was also investigated at baseline by measuring, using capillary gas chromatography, urinary xylose, mannitol and lactulose after oral challenge. Compared to controls, urinary neopterin was significantly increased in patients with non-small cell lung carcinoma. No significant change in urinary neopterin was observed during the therapy with gefitinib. A significant correlation was observed between urinary neopterin and xylose absorption (rs = -0.58, p <0.05), lactulose/mannitol (rs = 0.75, p <0.01), and lactulose/ xylose (rs = 0.62, p <0.05) ratios. In conclusion, EGFR blockade had no effect on systemic immune activation, evaluated with urinary neopterin. A significant correlation has been observed between urinary neopterin and parameters of intestinal permeability and absorption.

Preliminary Evidence on the Direction of Effects Between Day-to-Day Changes in Cellular Immune Activation, Fatigue and Mood in a Patient with Prior Breast Cancer: A Time-Series Analysis Approach

Abstract This study on a patient with prior breast cancer investigated the cause-effect relations between immune system activation, fatigue and mood under real-life conditions. The 60-year old woman (primary diagnosis 5 years ago, relapse one year ago, currently no signs of recurrence) collected her entire urine for 31 days in 12 hour intervals for the determination of immune activation marker neopterin and creatinine concentrations by HPLC. This study used only the daytime urinary neopterin concentrations (from approx. 8 a.m. to 8 p.m.) and cross-correlated them with daily data from mood (3-Skalen-EWL) and fatigue (VAS) questionnaires which the patient filled in for 31 days. Serial dependencies were controlled for by applying moving average smoothing. When averaged over the whole observation period, daily fatigue, daily mood and daily urinary neopterin (average 173 μmol per mol creatinine) were within normal limits. Cross-correlational analyses revealed that increases in urinary neopterin significantly preceded increases in fatigue by 24 hours (lag 1: r = +0.424; p <0.05). The opposite direction of effects, however, existed between mood and neopterin, i.e., decreases in mood preceded increases in neopterin by 96 hours (lag 4: r = −0.697; p <0.05). The results in this patient suggest a disturbed stress system activity where negative emotions are associated with increases instead of decreases in the degree of cellular immune activation and where cellular immune activation may trigger central nervous system symptoms such as fatigue. Despite some restrictions in data quality this study shows the feasibility of gathering evidence on naturally occurring psychoimmunological cause-effect relations based on extensive serial data collection and time series analysis.

Urinary Neopterin in Patients with Ovarian Cancer

Abstract Urinary neopterin, an indicator of systemic immune activation, is increased in most patients with epithelial ovarian carcinoma (EOC) and is an independent prognostic indicator. The data on prognostic significance of neopterin in EOC have been collected before the advent of paclitaxel that has changed the management and natural history of the disease. In the present study, we have evaluated the prognostic significance of urinary neopterin in 49 patients with primary and secondary ovarian neoplasms treated in the late 1990s and in 2000s. Urinary neopterin was measured by high-performance liquid chromatography. Compared to controls, urinary neopterin was significantly increased in patients with both primary ovarian cancer and ovarian metastases of other tumors (341 ± 343, and 328 ± 277 vs. 133 ± 40 μmol/mol creatinine; p <0.001 ). Serious toxicity of chemotherapy was observed in 8 out of 12 (67%) patients with urinary neopterin equal or above 338 μmol/mol creatinine (mean of all patients) compared to 2 of 19 ( 11%) of patients with urinary neopterin below 338 μmol/mol creatinine (Fisher exact test, p - 0.001). No significant changes were observed in urinary neopterin concentrations during the treatment with paclitaxel/platinum. A significant correlation was observed between urinary neopterin and percentage of xylose absorbed (rs = -0.58, p = 0.03), and positive correlations were observed between urinary neopterin and lactulose/ mannitol (rs = 0.63, p = 0.02), lactulose/xylose (rs = 0.79, p = 0.0007) and sucrose/xylose (rs = 0.60, p = 0.02) ratios. Survival was significantly longer in patients with urinary neopterin below 338 μιηοΐ/ιτιοί creatinine in the whole group of 49 patients with ovarian cancer, in 36 patients with primary ovarian cancer as well as in 13 patients in ovarian metastases of other primary tumors. A significant difference in survival was also observed when 37 pretreated patients or 24 pretreated EOC patients were evaluated (p = 0.05). In conclusion, neopterin remains a significant prognostic indicator in patients with recurrent ovarian cancer in the era of newer chemotherapeutic agents. Increased urinary neopterin was associated with chemotherapy toxicity.

Systemic Immune Activation, Anemia and Thrombocytosis in Breast Cancer Patients Treated by Doxorubicin and Paclitaxel

Abstract Increased urinary concentrations of neopterin, an indicator of systemic immune activation, have been reported only in a minority of patients with breast cancer. We determined urinary neopterin by high-performance liquid chromatography in 78 patients with breast carcinoma, including 51 patients treated by systemic administration of doxorubicin and paclitaxel. Urinary neopterin before the therapy was not statistically different in patients compared to controls. Increased neopterin concentrations were more frequent in patients with advanced disease. A statistically significant increase in urinary neopterin, gradual decrease in hemoglobin and an increase in platelet counts were observed during doxorubicin/paclitaxel chemotherapy. The concentration of urinary neopterin before the second cycle of chemotherapy has shown significant negative correlation with the concentrations of hemoglobin later in the course of chemotherapy and a positive correlation with platelet counts. In conclusion, urinary neopterin is normal in most patients with breast cancer. Increased urinary neopterin concentrations during doxorubicin/ paclitaxel chemotherapy indicate the presence of systemic immune activation that seems to be associated with chemotherapy-induced anemia and thrombocytosis.

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.

Urinary Neopterin in Patients with upper Gastrointestinal, Biliary and Pancreatic Carcinomas

Abstract Increased urinary neopterin has been associated with advanced disease and poor prognosis in patients with colorectal carcinoma, but less is known about urinary neopterin in other gastrointestinal tumors. We have investigated urinary neopterin in 53 patients with carcinomas of the upper gastrointestinal tract, pancreas and biliary tract. Conipared to controls, urinary neopterin was increased in patients with gastric carcinoma, pancreatic Carcinoma, cholangiocarcinoma and gallbladder carcinoma. Urinary neopterin was a significant prognostic indicator of survival in univariate as well as multivariate analyses. No significant change in urinary neopterin concentrations was observed during the short follow-up, but increased urinary neopterin concentration at the end of followup was associated with poor prognosis. In conclusion, significantly increased urinary neopterin concentrations were observed in the present cohort of patients. Urinary neopterin is an independent prognostic indicator in patients with carcinomas of the upper gastrointestinal tract, biliary tree and pancreas.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-γ induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+T-cell numbers.

Method for urinary neopterin measurements by HPLC

To the Editor: In the June 2004 issue of the Journal, Drs. Ribeiro de Castro and coworkers described a new method to determine neopterin concentrations in urine by HPLC and UV-absorption detection [de Castro MR, Di Marco GS, Arita DY, Teixeira LC, Pereira AB, Casarini DE. Urinary neopterin quantification by reverse-phase high-performance liquid chromatography with ultraviolet detection. J Biochem Biophys Methods 2004;59:275–83 [1]]. Although simple and rapid, unfortunately this report does not consider any possible analytical complications known from the biochemistry of neopterin. The major problem with this method is that the authors did not at all consider possible interferences with related compounds.

Effect of ionizing radiation on the pteridine metabolic pathway and evaluation of its cytotoxicity in exposed hospital staff

Investigations carried out to estimate the effect of long-term occupational exposure to low levels of external ionizing radiation indicated that exposed hospital staff showed an increase in chromosome aberrations. The purpose of this study was to evaluate whether genomic instability or an alteration in pteridine synthesis could be used as a marker of the potential hazard of ionizing radiation in hospital workers. Twenty γ-radiation- and 33 X-ray-exposed technicians working in radiotherapy and radio-diagnostic units were included in this study, along with 22 healthy matched individuals. Plasma concentrations of nitrite plus nitrate (NO x ) were measured to estimate reactive nitrogen species. Urinary neopterin, biopterin and creatinine concentrations were measured by high-performance liquid chromatography to determine metabolic activity along the pteridine pathway. Sister chromatid exchange was used as a measure of mutagenicity. Apoptosis was evaluated morphologically and also with a DNA-fragmentation test. The plasma NO x levels of both γ-radiation- and X-ray-exposed technicians were significantly higher than those of the healthy controls ( p < 0.05). While the urinary biopterin concentrations were significantly higher in radiation-exposed groups compared with the healthy subjects ( p < 0.05), urinary neopterin concentrations remained unchanged. The apoptosis rates of γ-radiation- and X-ray-exposed workers were significantly elevated in comparison with those in the control group (both p < 0.05). Also, the increase in sister chromatid exchange frequency was significant in each of the radiation-exposed groups (exposed groups versus controls; p < 0.05). These results indicate that long-term exposure to low-dose ionizing radiation, even below the permitted levels, could result in increased oxidative stress, which may lead to DNA damage and mutagenicity.

Urinary Neopterin Levels in the Different Stages of Pregnancy

Background/Aims: Neopterin is a biochemical marker of activated cell-mediated immune response which increases in pathological conditions associated with cellular immune activation as well as in pregnancy where cellular immune response is predominant. The aim of this study was to determine the urinary neopterin level in each trimester of pregnancy and to determine if it can be used as a marker. Methods: 104 healthy pregnant women (mean age 22.10 ± 4.39 years; 36 in the first, 30 in the second and 38 in the third trimester) and 16 non-pregnant healthy women (mean age 20.94 ± 4.48 year) were included. Results: The mean urinary neopterin concentration of all pregnant women was higher than that of non-pregnant women (166.4 ± 31.7 and 103.1 ± 27.5 µmol/mol creatinine respectively, p < 0.01). The mean urinary neopterin levels in each trimester and non-pregnant women were 139.8 ± 49.6, 131 ± 40.2, 227.9 ± 86.5 and 103.1 ± 27.5 µmol/mol creatinine, respectively. Urinary neopterin levels were not significantly different between non-pregnant, first and second trimester groups, but were significantly higher in the third trimester than each of these groups (p < 0.05, p < 0.01 and p < 0.01 respectively). Conclusion: Urinary neopterin levels increase significantly in the third trimester probably due to more predominated cellular immunity. The pathologies causing cellular immune activation, especially in the first two trimesters can be predicted with urinary neopterin levels.

Effect of Aluminum Exposure on Pteridine Metabolism

Occupational and environmental aluminum (Al) exposure cause serious health problems by interaction with biological systems. Al is one of the most documented metals because its cellular targets are unclear biochemical processes and membranes of organisms. The major aim of the present study was to investigate the alteration of serum and urine aluminum in occupational exposure and to observe whether the metal exposure could cause any changes in pteridine-pathway-related critical compounds such as urinary neopterin and biopterin and blood dihydropteridine reductase (DHPR). In this study, determination of the metal concentrations was carried out in Al-exposed workers (n=23) and healthy volunteers (n=18) by using atomic absorption spectrometer. DHPR enzyme activity and levels of neopterin and biopterin were detected by spectrophotometric and high-performance liquid chromatographic methods, respectively. It was found that occupational exposure to the metal led to a statistically significant increase in serum Al levels compared to the controls (p<0.05). At the same time, urinary neopterin and biopterin concentrations of the exposed group were higher than nonexposed subjects (both p<0.05). The correlations among Al levels and DHPR activity, magnesium concentration in serum and urine, working years, smoking status, and age were evaluated.

Urinary neopterin concentrations in patients with Balkan endemic nephropathy (BEN)

Balkan endemic nephropathy (BEN) is of great clinical importance in restricted areas of Bulgaria, Serbia, Croatia, Bosnia, Herzegovina, and Romania, since the etiology of BEN is still unknown. In urine samples from 48 patients (41 females and 7 males, aged 65.6 +/- 6.87 years) with BEN living in an endemic area of Vratza district, Bulgaria, neopterin concentrations were measured by high-pressure liquid chromatography (HPLC) and compared with other clinical and laboratory investigations, including creatinine, hemoglobin, and erythrocyte sedimentation rates (ESRs). Urinary neopterin concentrations were 263 +/- 128 (mean +/- SD; range, 78 to 786 micromol/mol creatinine), 24 (50%) of BEN patients presented with increased concentrations as compared to the established normal ranges. Average ESRs were increased (1 hour, 29.0 +/- 14.7 mm/hour) and hemoglobin was decreased (109.3 +/- 16.4 g/L). Hemoglobin correlated inversely with ESRs (rs = -0.787 and -0.780) and creatinine concentrations (r = -0.690, all P < 0.001), but not with neopterin concentrations. Neopterin concentrations also did not correlate with serum creatinine levels. There existed an age relationship of ESR, creatinine, and hemoglobin, but not of neopterin. Neopterin concentrations were slightly lower in five females with low titers of antibodies against local B1 hantavirus strain (P < 0.05). The findings can support an immune-mediated inflammatory process in the pathogenesis of BEN only in a subgroup of patients.

Colchicine derivatives inhibit neopterin production in human peripheral blood mononuclear cells (PBMC).

Colchicine is a microtubule disrupting agent, mostly used as treatment in various kinds of inflammatory diseases such as acute familial Mediterranean fever and Behcet's disease, as well as gout. In patients with familial Mediterranean fever treatment with colchicine induces a decline of urinary neopterin concentrations which indicates a decrease of cell-mediated immune activation. In this study, we investigated a potential effect of colchicine on the T cell/macrophage system in vitro. The human myelomonocytic cell line THP-1 and PBMC were treated with colchicine or the colchicine derivative, colcemide, in the presence or absence of 250 U/ml interferon-gamma (IFN-gamma) or 10 microg/ml lipopolysaccharide (LPS) for 48 h or 96 h. Colchicine and colcemide increased neopterin/protein production in unstimulated THP-1 cells, but no such effect was apparent in cells stimulated with IFN-gamma. By contrast, when PBMC were treated with colchicine or colcemide a significant reduction in neopterin formation was evident in cells without and with prestimulation by IFN-gamma or LPS. In parallel, reduced production of IFN-gamma was observed in PBMC. These data suggest that colchicine and colcemide are able to inhibit T cell activation within the cellular immune response.

Follow-up of Urinary Neopterin Concentrations in two Healthy Children until Adolescence

Abstract Neopterin is a sensitive marker of the activated cellular (= Thl-type) immune response. Neopterin concentrations in healthy children are higher compared with those of adults and are declining with increasing age. In this study, we present a follow-up of urinary neopterin to creatinine concentrations in two healthy children until adolescence. Data were available from one female (7 - 23 years) and her brother (0 - 18 years), of whom early morning urine specimens were collected on an irregular basis throughout 18 years. In total, neopterin and creatinine concentrations were measured by high pressure liquid chromatography (HPLC) in 343 urinary specimens. In both children, concentrations of urinary neopterin were highest at study entry. With increasing age neopterin concentrations decreased continuously to reach rather constant levels around the age of fifteen years. On several occasions at which individuals presented with common sickness, mostly of infectious origin, neopterin concentrations were found highly increased. In the absence of such infectious episodes, neopterin/creatinine measurements of both individuals fit well to previously established normal ranges. However this was true only for specimens collcctcd when children were older than 10 years, before that age concentrations of neopterin were frequently found to be higher than the established upper limits of the normal range.

Urinary Neopterin Concentrations in Healthy Individuals with Household Contact

Abstract Increased neopterin concentrations in serum and urine indicate activation of cell-mediated immunity. In this study, urinary neopterin concentrations of a family consisting of 1 child (aged 5 years), her parents, and her grandparents were determined over a one year period and the course of neopterin levels was compared. Urine specimens were taken every second week during 1 year beginning in June. All 5 individuals lived in the same house, child and her parents separated by one floor from the grandparents. Neopterin concentrations were determined by high Performance liquid chromatography. In adults, neopterin concentrations were very stable throughout the year and peak increases occurred only rarely. In contrast, 5 sharp peaks of urinary neopterin concentrations were observed in the child, all occurring during the period when she was attending the kindergarten. Comparing the course of neopterin concentrations between the persons tested, several corresponding elevations of urinary neopterin were detected in the child and her relatives. The best association was detected between the child and her father (3 peaks of neopterin concentrations were observed, 1 of which coinciding with a peak in the child and two peaks with two weeks delay in the father). Between the child and her mother 1 corresponding neopterin peak was observed. One highly increased urinary neopterin concentration was observed in the grandmother which corresponded to a peak in the child with two weeks delay, a similar Observation was made between the child and her grandfather. In summary, high degree of correspondence in neopterin peaks was detected between child and adults. The data render it likely that the child was transmitting infectious diseases which she acquired at the kindergarten to her relatives, and the data are in line with the assumption that a dose family contact between individuals increases the risk of infectious disease transmission via household contact.

Neopterin as a marker of immunostimulation: an investigation in anaesthetic workplaces.

Personnel working in operating theatres and recovery rooms are exposed to a variety of noxious substances. The results of studies of the effects of occupational exposure on immune parameters are conflicting. Neopterin is an acknowledged marker of immunostimulation. Urinary neopterin levels of 58 anaesthetists and anaesthetic nurses were measured over a 3-week period. Neopterin analyses were performed using high performance liquid chromatography. Neopterin levels were within the normal range for all subjects. Younger subjects (aged < or = 35 years) had significantly higher urinary neopterin concentrations than older subjects (aged > 35 years). The present study is the first to investigate the influence of anaesthetic exposure on neopterin levels. No evidence of immunostimulation was found.

Urinary Neopterin Indicates Early Infection and Disease Progression: Model Studies with Simian and Human Immunodeficiency Viruses in Macaques

Abstract The value of urinary neopterin as a predictive marker for disease progression in SIV- and HIV-2-infected rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) was assessed by comparing pre- with postinfection data. Before infection stable baselines for neopterin were observed in both species with significantly higher concentrations in cynomolgus macaques than in rhesus macaques. After infection of cynomolgus macaques with human immunodeficiency virus type 2 (HIV-2) neopterin concentrations exceeded 1.2 - 4.2 times preinfection values, whereas rhesus monkeys infected with simian immunodeficiency virus (SIV) yielded concentrations of more than 8 times above baseline. Increased neopterin concentrations always preceded seroconversion. No rise of neopterin was observed in cynomolgus macaques remaining seronegative after inoculation with HIV-2, whereas after inoculation with SIV neopterin was slightly elevated in rhesus monkeys despite remaining seronegative. In animals with high virus replication a pronounced increase of neopterin levels was followed by signs of immunodeficiency. Therefore like in HIV-1-infected man, in macaques infected with SIV or HIV-2 the urinary neopterin concentration is an early and reliably predictive marker for AIDS disease progression and reflects pathogenicity. This parameter can be easily assessed in study protocols for drug and vaccine tests in monkeys as in man.

Association between homocysteine and neopterin in healthy subjects measured by a simple HPLC-fluorometric method

Objectives: Neopterin and homocysteine promote vascular smooth muscle cell proliferation through the activation of nuclear factor κ B. The aim of this study was to investigate the relation between these two compounds in healthy subjects by a rapid HPLC-fluorometric method which simplifies sample pretreatment for the measurement of neopterin in serum. Design and methods: In 40 healthy subjects (45.9 ± 2.1 yr, mean ± SEM, 10 males, 30 females) serum neopterin concentrations were measured by HPLC-fluorometry and enzyme-linked immunusorbant assay-ELISA and the results were compared. Urinary neopterin and plasma total homocysteine concentrations were assayed by HPLC-fluorometry. Results: Serum neopterin concentrations measured by HPLC and ELISA were 7.5 ± 0.4 and 7.4 ± 0.3 nmol/L, respectively, r = 0.92, p < 0.01. Urinary neopterin level was 163.9 ± 11.0 nmol/mmol creatinine and plasma total homocysteine 7.6 ± 0.4 μmol/L. A significant positive correlation was observed between serum neopterin and plasma total homocysteine (r = 0.59, p < 0.01). Conclusions: A simple and rapid sample pretreatment for the measurement of neopterin in serum has been introduced. The significant positive correlation between neopterin and homocysteine implies that, interference with leukocyte function might be a new possible mechanism for the deleterious effects of homocysteine on vascular function.