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PubMed2005

Serum neopterin, tumor necrosis factor-alpha and soluble tumor necrosis factor receptor II (p75) levels and disease activity in Egyptian female patients with systemic lupus erythematosus.

OBJECTIVE: To determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-alpha (TNF-alpha) and soluble tumor necrosis factor receptor II (p75) (sTNFRII) in patients with systemic lupus erythematosus (SLE), manifested clinically with lupus nephritis (LN), neuropsychiatric lupus erythematosus (NPLE), and/or vasculitis compared with established parameters (complements C3 and C4). PATIENTS AND METHODS: Serum concentrations of neopterin, TNF-alpha and sTNFRII were studied in 40 female patients with SLE at various degrees of disease activity and in 10 healthy controls, matched for age and sex, using an ELISA kit. Disease activity was assessed by the SLE disease activity index (SLEDAI) score. Thirty-five, 30 and 28 of our patients presented with LN, NPLE and/or vasculitis, respectively, as the main clinical manifestation. RESULTS: Serum levels of neopterin, TNF-alpha and sTNFRII were significantly increased, while the TNF-alpha/sTNFRII ratio, C3 and C4 levels of SLE patients were significantly lower than those of healthy controls. Neopterin and sTNFRII were the only parameters that showed significantly higher levels in SLE patients with mild activity compared to normal subjects and were the only parameters that showed a significant elevation in membranous nephritis and in mild NPLE compared to patients without nephritis and NPLE. Patients with vasculitis had significant elevation of serum neopterin, TNF-alpha and sTNFRII levels compared to patients without vasculitis. We found significant correlations between all measured variables and the SLEDAI score. Also, serum neopterin levels showed significant positive correlation with serum TNF-alpha, sTNFRII and TNF-alpha/sTNFRII levels. Serum neopterin and sTNFRII could be used to identify SLE patients from normals with a sensitivity and specificity of 100%. Multivariate linear regression analysis showed that serum sTNFRII was the only significant independent variable among parameters for prediction of SLE disease activity. CONCLUSION: We suggest that serum sTNFRII and neopterin are more sensitive markers of disease activity than TNF-alpha, C3 or C4. However, sTNFRII may be a clinically useful independent marker for prediction of SLE disease activity and to differentiate normal subjects from those having mild SLE.

Case-Control Studies↗
PubMed2006

Detection of serum neopterin for early assessment of dengue virus infection.

OBJECTIVE: Neopterin is generated and released in increased amounts by macrophages upon activation by interferon-gamma during Th1-type immune response. The potential usefulness of neopterin in early prognostic information of dengue virus infection was investigated. METHODS: Neopterin concentrations were determined in serum samples from 110 dengue fever (DF) patients. The neopterin levels were compared with those in 50 measles and 40 influenza patients; 155 healthy blood donors served as controls. RESULTS: In acute sera of DF patients mean neopterin concentration was 48.2 nmol/L, which was higher than that in patients with measles (mean: 36.3 nmol/L) and influenza (18.8 nmol/L) and in healthy controls (6.7 nmol/L; P<0.001). In the patients with confirmed DF, an early neopterin elevation was detected already at the first day after the onset of symptoms and rose to a maximum level of 54.3 nmol/L 4 days after the onset. Higher increase of neopterin level in DF patients was associated with longer duration of fever and thus predicted the clinical course of the disease. CONCLUSIONS: Neopterin concentrations were found significantly higher in DF patients compared with healthy controls and also with other viral infections (P<0.001) and may allow early assessment of the severity of DF.

Adolescent↗
PubMed2006

Cognitive deterioration in Alzheimer's disease is accompanied by increase of plasma neopterin.

The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer's disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-gamma. Forty-three probable AD patients were investigated at baseline and follow up (14.5+/-0.5 months; mean+/-s.e.m.). We assessed the clinical progression by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery and compared cognitive changes to serum concentrations of neopterin, C-reactive protein (CRP) and antibody to cytomegalovirus (CMV). The mean neopterin concentrations increased significantly from 9.8+/-1.0 to 13.6+/-2.1 nM (p=0.04). In contrast, mean CRP concentrations at baseline was 0.46+/-0.1 and non-significantly decreased to 0.28+/-0.04 mg/dl. Of AD patients 70% were CMV IgG-seropositive at baseline and CMV-antibody concentrations correlated with levels of neopterin (Spearman r=0.386, p=0.016). CERAD scores did not correlate with any of immune parameters at baseline. At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression (r=-0.353, p<0.05 and r=-0.401, p<0.01, respectively). Subdividing the sample with respect to baseline MMSE scores, neopterin concentrations significantly increased only in the group of MMSE<20. In the multiple testing covariated for age, gender, Apolipoprotein E-epsilon4 allele, time difference between both measurements, neopterin remained significantly associated with cognitive decline. In summary, neopterin concentrations correlated with cognitive decline in AD patients, which might be due to high CMV seropositivity in that population.

Aged↗
PubMed2005

Neopterin in HIV-1 infection.

Neopterin is well established as a reliable marker in HIV-1 infection. Neopterin concentrations measured in urine or serum indicate sensitively the course and progression of the disease as well as efficacy of anti-retroviral therapy. The main trigger for neopterin production is Th1-type cytokine interferon-gamma. During acute HIV-1 infection, enhanced formation of neopterin occurs already at a very early time point, before antibody seroconversion takes place. After this stage, neopterin concentrations in serum and urine closely correlate with virus load in the circulation of HIV-1-infected patients. Data provide evidence for an important role of immune activation and Th1-type cytokine interferon-gamma in the pathogenesis of HIV-1 infection. This review subsumes the importance of neopterin as a marker in HIV-1 infection. Further evidence is increasing, that neopterin derivatives might modulate immune response by interfering with the cellular redox balance, activating redox-sensitive transcription factors, or inducing apoptosis in specific cell types. The possible impact of neopterin derivatives and of other biochemical pathways induced by interferon-gamma such as indoleamine 2,3-dioxygenase in chronic diseases like HIV-1 infection is discussed.

Apoptosis↗
PubMed2001

Neopterin production in SCID mice injected with human peripheral blood mononuclear cells.

Intraperitoneal transfer of peripheral blood mononuclear cells (PBMC) from human EBV+ donors into severe combined immunodeficiency (SCID) mice is a suitable model for studying some aspects of lymphomagenesis and immune activation. Neopterin is a soluble immune marker which was found to be a useful indicator for immune activation processes in humans, e.g. to monitor immunological complications in allograft recipients or to predict prognosis in HIV-infected individuals. In contrast, this pteridine compound is normally synthesized in murine organism in only very low amounts. The measurement of neopterin concentrations in serum and urine should be feasible in SCID mice reconstituted with human PBMC. In this study, we examined the usability of this experimental model for monitoring human T cell activation by neopterin measurements. The production of neopterin by SCID mice after injection of freshly isolated human PBMC, purified B or T cells and cultured Epstein-Barr virus (EBV)+ lymphoblastoid cells (LCL) was determined. It was found that neopterin can be detected early after injecting SCID mice with PBMC, whereas injection of purified human T or B cells did not result in neopterin production. Highest neopterin levels were detected in mice treated with LCL cells when developing lymphoma. We discuss the possible sources of neopterin along this process and its usefulness in this model.

Animals↗
PubMed1985

Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis.

In previous publications we showed that neopterin, a pyrazino-pyrimidin compound, represents a biochemical marker for the assessment of cellular immune responses. We thought that the evaluation of this marker molecule might enable insight into the activity of cellular immune responses underlying ulcerative colitis (UC). Evaluation of urinary neopterin excretion in 25 consecutive untreated UC patients revealed striking correlations between neopterin levels and the severity of disease: elevated levels were observed in 9 out of 9 patients with moderately severe to severe, in 3 of 4 with mild and in none of 12 patients with quiescent disease. Further evidence for a correlation between disease activity and neopterin excretion was obtained on the basis of long-term follow-up studies performed in 4 cases. These studies indicated normalization of neopterin levels when clinical remission was achieved. Thereafter, the relative significance of neopterin excretion for determination of clinical stage was assessed by linear correlation analyses and was compared with conventional clinical parameters such as anemia, number of motions per day, raised temperature, ESR and extent of bowel involvement. The logarithm of neopterin excretion and the extent of bowel involvement were the two single parameters most closely related to the clinical stage of ulcerative colitis. We, therefore, conclude that evaluation of neopterin excretion in ulcerative colitis patients represents a new and useful tool for the clinical monitoring of disease activity.

Adolescent↗
PubMed1997

Increased neopterin in patients with chronic and acute coronary syndromes.

OBJECTIVES: The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes. BACKGROUND: In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate-biopterin pathway, is a marker for those activated macrophages. METHODS: We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 +/- 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. RESULTS: In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p < 0.0001). Values also differed significantly between patients with CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p < 0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period. CONCLUSIONS: Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

Adult↗
PubMed1989

Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1.

Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features.

Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P less than 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs = -0.61, P less than 0.005 and rs = -0.83, P less than 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs = -0.58, P less than 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.

Adolescent↗
PubMedDate not supplied

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.

Adult↗
PubMed1995

Gastric juice neopterin in Helicobacter pylori infection.

Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori, a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 +/- 15.6 vs. 2.1 +/- 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 +/- 12.0 vs. 11.1 +/- 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 +/- 3.2 vs. 1.3 +/- 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 +/- 4.6 vs 1.6 +/- 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.

Adolescent↗
PubMed2005

Gamma interferon is dispensable for neopterin production in vivo.

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-gamma). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-alpha and/or IFN-beta. However, it is unknown if any IFN-gamma-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-gamma production or function due to severe mutations in molecules involved in IFN-gamma/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-gamma activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-gamma-, IL-12-, and IL-23-dependent pathway defects.

Adolescent↗
PubMed1995

Serum neopterin concentrations in chronic liver disease.

Neopterin is produced by macrophages after stimulation with interferon gamma or lipopolysaccharide. Its production is increased in many infectious, autoimmune, and malignant diseases. The aim of this study was to examine whether, on the basis of neopterin as a marker, liver diseases could be classified according to aetiology and stage of disease. A cohort of 264 patients with chronic liver diseases (viral, metabolic, autoimmune, toxic) and 150 normal controls were studied; 136 of the patients had cirrhosis. Increased serum neopterin concentrations were found in 41% of all patients (controls 6.0 (2.2) nmol/l), with patients in the cirrhotic stage of disease showing higher neopterin values (mean (SD) 15.7 (23.6) nmol/ml) than those in the non-cirrhotic stage (9.9 (5.5)). There were no statistically significant differences in the serum neopterin concentrations that could be considered characteristic for different stages of disease classified according to the Child criteria. Such differences in concentrations of neopterin that were found in patients with liver diseases grouped according to underlying causes were only marginal. Serum neopterin concentrations were found to be significantly lower than in any other disease group only in patients with Wilson's disease. The results suggest that activated macrophages participate in the development of chronic liver disease. Measurement of serum neopterin does not offer a reliable method for differentiating between various aetiologies of chronic liver diseases and does not help to predict severity of cirrhosis.

Biopterins↗
PubMed2000

Increased serum neopterin: a marker of coronary artery disease activity in women.

OBJECTIVE: To assess whether neopterin concentrations in women with unstable angina differ from those in women with chronic stable angina. DESIGN: Prospective cohort study. SETTING: University hospital in south west London. PATIENTS: 114 consecutive women with angina were studied: 82 had chronic stable angina (typical exertional chest pain, positive exercise ECG testing, and/or abnormal myocardial scintigraphy; symptoms stable for at least three months), and 32 had unstable angina (Braunwald class III). All patients with chronic stable angina (100%) and 18 with unstable angina (56.3%) underwent digital coronary angiography; neopterin concentrations were determined using a commercially available immunoassay. MAIN OUTCOME MEASURES: Major clinical events during one year follow up were readmission with Braunwald's class IIIb unstable angina, non-fatal myocardial infarction, and cardiac death. RESULTS: Major events occurred in 12 women with chronic stable angina (14.6%) and nine women with unstable angina (28.1%). Mean (range) neopterin concentrations were significantly higher in women with unstable angina than in those with chronic stable angina (7.6 (5.1-11.5) nmol/l v 5.9 (4.4-7.5) nmol/l; p = 0.003), even after adjustment for variables which were significantly different on univariate analysis. In women with chronic stable angina, baseline neopterin concentrations were higher in those with cardiac events than in those without events (7.1 (5.9-9.1) nmol/l v 5.7 (3.9-7.3 nmol/l); p = 0.010), even after adjustment for variables with significant differences between both groups on univariate analysis. CONCLUSIONS: On average, women with unstable angina had significantly higher neopterin concentrations than women with chronic stable angina. Women with chronic stable angina with events during follow up had higher neopterin concentrations than those without events. Neopterin concentrations were similar in patients with unstable angina and women with chronic stable angina who developed events. Neopterin concentrations may therefore be a marker of risk in women with coronary artery disease.

Aged↗
PubMed2000

Urinary N-acetyl-beta-D-glucosaminidase and neopterin aid in the diagnosis of rejection and acute tubular necrosis in initially nonfunctioning kidney grafts.

AIM: The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. METHODS: Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN, 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was applied to compute diagnostic performance and an optimal discriminating threshold. RESULTS: Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 +/- 1.0 U/mmol urinary creatinine; neopterin 270 +/- 126 nmol/mmol urinary creatinine; mean +/- SD) as compared with the ATN group (NAG 12 +/- 10 U/mmol, p < 0.001 vs. control group; neopterin 303 +/- 195 nmol/mmol, n.s.) and the rejection group (NAG 7 +/- 8 U/mmol, p < 0. 01; neopterin 508 +/- 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimension nmol neopterin/U NAG activity) increased during rejections as compared with ATN (139 +/- 74 vs. 50 +/- 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 +/- 0.07 (p < 0.001). Applying a ROC-estimated optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection episodes were classified correctly. CONCLUSION: The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants.

Acetylglucosaminidase↗
PubMed1986

Serum levels of neopterin as related to the prognosis of human prostatic carcinoma.

In 93 patients suffering from prostatic cancer, serum levels of neopterin, a pteridine reflecting activation of the immune defence system, were measured at the time of diagnosis and 6 and 12 months after treatment with orchidectomy or estrogens. Neopterin levels were initially greater than 10 nM/l in 27% of the patients and in this group tumor recurrences occurred in 28% as compared to 7% in the group with neopterin less than 10 nM/l. No apparent correlation between tumor stage and grade and neopterin levels could be demonstrated. Neopterin levels decreased significantly after onset of treatment (p less than 0.001), which implicates a hormone dependence. But still patients with initially elevated serum neopterin levels, and thus an assumed activated immune defence system at the time of diagnosis, had lower survival rates than those without elevated neopterin levels (p less than 0.001). It is concluded that elevated levels of neopterin in serum is a sign of poor prognosis in human prostatic cancer.

Aged↗
PubMed2001

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

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed1999

Neopterin serum levels in pancreatic adenocarcinoma.

CONCLUSIONS: Activation of the immune system in pancreatic cancer is demonstrated by increased serum levels of neopterin, soluble Interleukin 2 receptor (sIL-2R), and Interleukin 6 (IL-6). Determination of these parameters does not provide benefit in the diagnosis of pancreatic cancer. BACKGROUND: The aim of the study was to define the diagnostic value of serum neopterin, an in vivo marker of macrophage activity, in pancreatic cancer. METHODS: Thirty-four patients with pancreatic cancer were studied. According to the UICC TNM classification 6 were in stage I, 9 in stage II, 6 in stage III, and 13 in stage IV. Twenty-four patients with chronic pancreatitis, 72 healthy blood donors, and 20 patients with jaundice resulting from gallstones were used as control groups. Neopterin, tumor necrosis factor (TNF), sIL-2R, and IL-6 were measured in serum in the different groups; Ca 19-9 was also measured in cancer and pancreatitis. RESULTS: Serum levels of neopterin, sIL-2R, and IL-6 were higher in cancer than in pancreatitis and healthy donors, and in pancreatitis higher than in donors. Serum TNF was similar in the three groups. Serum levels of neopterin, TNF, sIL-2R, and IL-6 were not related to the tumor stage or to Ca 19-9 levels. A positive correlation was found between sIL-2R and neopterin levels. Neopterin levels in obstructive jaundice were similar to those of pancreatitis. Ca 19-9 at the recommended cutoff of 37 U/mL showed the best sensitivity and specificity (88.2 and 87.5%, respectively). At the selected cutoff neopterin, TNF, sIL-2R, and IL-6 showed low sensitivity and specificity in differentiating cancer from pancreatitis.

Adenocarcinoma↗