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PubMed1994

Factors influencing serum neopterin and beta 2-microglobulin levels in a healthy diverse population.

Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2-microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels.

Adult↗
PubMed2002

Acute cytomegalovirus infections in blood donors are indicated by increased serum neopterin concentrations.

In Austria serum neopterin measurement was introduced as an additional unspecific screening marker for the detection of routinely unscreened viral infections in blood donations in 1994. This study was performed to test for associations between serum neopterin concentrations in blood donations and cytomegalovirus infections of the donors. All consecutive blood donations from volunteer blood donors collected during 1 year were incorporated into the study. Serum neopterin concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and each donation of donors with CMV seronegativity or unknown CMV status was also screened for CMV antibodies by CMV IgG/IgM antibody ELISA. Data of donors who had two or more donations within this period were retrospectively analyzed for CMV seroconversions. CMV seroconversion was defined as a change in the donor's CMV status from antibody negative to positive. Frozen, stored plasma samples of the matching donors were tested for CMV IgM antibodies to confirm seroconversion. CMV seroconversions were classified by antibody patterns. In total, 56,068 consecutive blood donations were given by 44,427 volunteer donors. Among these, 9,105 had more than one donation during the observation period, and 4,329 (47.5%) out of these repeated donors were initially CMV antibody negative, of whom 36 were recruited as candidates for CMV seroconversion; 20 conversions were confirmed. All early infections ( n=8) were associated with neopterin concentrations of more than 13 nmol/l (98th percentile of all donations = 12.1 nmol/l) and all donations were excluded from transfusion solely on the basis of their elevated neopterin level. In addition, 17% of late and carrier states ( n=12) showed elevated neopterin concentrations. Acute CMV infections among blood donors presented with elevated serum neopterin concentrations even before CMV IgG/IgM antibodies were detectable.

Acute Disease↗
PubMed2006

Influence of neopterin and 7,8-dihydroneopterin on the replication of Coxsackie type B5 and influenza A viruses.

Pteridine derivatives neopterin and 7,8-dihydroneopterin are produced by human macrophages and dendritic cells upon stimulation with interferon-gamma (IFN-gamma) and therefore become detectable in increased amounts in humans during cell-mediated (Th1-type) immune response. Compounds produced upon influence of cytokine IFN-gamma often exert antiproliferative and antiviral activity. The aim of this study was to investigate the effect of neopterin and 7,8-dihydroneopterin on the replication of Coxsackie type B5 and influenza A viruses. The changes in the replication of these viruses were evaluated by the degree of cytopathic effect and their ability to form plaques in Coxsackie B5-infected human larynx carcinoma epithelial (Hep-2) cells and in influenza A-infected canine kidney epithelial cells (MDCK). Potential toxicity of neopterin and 7,8-dihydroneopterin was estimated by the incorporation of (3)H-thymidine and (3)H-uridine into Hep-2 and MDCK cells. Whereas 30 nmol/l neopterin delayed the development of the cytopathic effect of Coxsackie B5 virus in Hep-2 cells (P < 0.01), 7,8-dihydroneopterin did not have any essential influence at any of the concentrations tested between 10 nmol/l and 1,000 micromol/l. However, 100-1,500 micromol/l 7,8-dihydroneopterin significantly suppressed the propagation of influenza A virus. Neopterin and 7,8-dihydroneopterin were practically nontoxic for Hep-2 and MDCK cells even at high microM concentration. Results suggest that the increased production of neopterin derivatives by activated macrophages and dendritic cells may represent part of the antiviral armature induced by IFN-gamma. The mechanisms of the inhibitory effects of neopterin and 7,8-dihydroneopterin on virus replication apparently are different.

Animals↗
PubMed1986

Urinary neopterin, a marker of clinical activity in patients with Crohn's disease.

Urinary neopterin excretion was measured in 34 patients with Crohn's disease. Neopterin excretion showed a significant correlation with disease activity using a clinical activity score. An interacting effect of previous medical or surgical therapy on neopterin excretion could be ruled out. Disease localization and extent did not exert any influence on neopterin excretion. Neopterin values were significantly correlated with disease duration, body weight and the presence of a palpable abdominal mass. Multiple stepwise regression analyses identified the combination of neopterin, hematocrit, weekly stool frequency, palpable abdominal mass and related symptoms as predicting clinical activity better than Crohn's Disease Activity Index (CDAI). Thus, neopterin determination may be introduced as an additional biochemical parameter in the assessment of disease activity.

Adolescent↗
PubMed1988

Urinary neopterin excretion in pulmonary sarcoidosis: correlation to clinical course of the disease.

Urinary neopterin levels were determined by high pressure liquid chromatography in 36 patients with pulmonary sarcoidosis. Values were above normal range in 69.4% of all patients. Neopterin excretion was significantly higher in radiologic types II/III than in type I disease (p = 0.0265, Mann-Whitney U-test). Urinary neopterin showed a weak, but significant inverse correlation to disease duration (r = -0.36; p = 0.034, Spearman's rank correlation). No significant correlation could be found between neopterin and the presence of pulmonary or extrapulmonary symptoms, vital capacity, forced expiratory volume in the first second, steroid treatment, and serum angiotensin converting enzyme. Follow-up studies revealed that worsening or improvement of chest X-ray findings was invariably accompanied by rising or decreasing neopterin excretion, respectively. Patients with normal neopterin at initial evaluation had a higher tendency towards spontaneous healing, and none of them deteriorated during the follow-up period. We conclude that urinary neopterin excretion reflects one aspect of alveolitic "activity" in pulmonary sarcoidosis and that normal values probably indicate a favorable prognosis.

Adult↗
PubMed1989

Neopterin and viral infections: diagnostic potential in virally induced liver disease.

D-erythro-neopterin is excreted in high amounts from human monocytes/macrophages responding to stimulation with gamma interferon. In vivo, the determination of neopterin offers a convenient possibility for monitoring the activation state of the cell-mediated immune system. Neopterin concentrations in body fluids also are raised with high sensitivity in viral diseases, irrespective of the specific nature of the virus. Thus, neopterin concentrations also are raised in viral diseases the causative agent of which has not yet been characterized such as non-A, non-B hepatitis. Determination of neopterin concentrations is easily accomplished by chromatographic or immunological techniques. Clinical studies showing the behaviour of neopterin levels in viral diseases are reviewed with special emphasis laid on the behaviour of neopterin concentrations in body fluids during virus-induced liver diseases, particularly non-A, non-B hepatitis. The possibilities offered by this marker to reduce the risk of disease transmission via transfusion of blood or blood components are discussed.

Biopterins↗
PubMed2005

Neopterin concentrations in blood donors differ between AB0 blood group phenotypes.

OBJECTIVES: Neopterin is produced by human monocyte-derived macrophages upon stimulation with interferon-gamma and is therefore a sensitive indicator for cellular immune activation. Common factors like age, diastolic blood pressure, body mass index, or smoking habits were found to be associated with neopterin concentrations in humans. DESIGN AND METHODS: In order to find possible genetic determinants which might influence neopterin production, we investigated 8288 consecutive blood donors after exclusion of samples suspicious of infections. RESULTS: Donors with blood group phenotype 0 had moderately, but significantly (P < 0.0001) higher neopterin concentrations (mean +/- SD: 6.94 +/- 1.52 nmol/L) than those with phenotype A (6.75 +/- 1.50 nmol/L), phenotype B (6.73 +/- 1.48 nmol/L), and phenotype AB (6.68 +/- 1.57 nmol/L). CONCLUSIONS: Neopterin levels are higher in donors with blood group phenotype 0 than in other phenotypes. Data point to a genetic background of different neopterin concentrations. However, alterations of neopterin levels were much less expressed than the changes known to occur during diseases with an activated immune response.

ABO Blood-Group System↗
PubMed2005

Procalcitonin and neopterin correlation with aetiology and severity of pneumonia.

OBJECTIVE: Clinical outcome of pneumonia depends on a multifaceted treatment approach. Not only diagnostic methods but also early indicators of the degree of inflammatory response can aid in therapeutic decisions. The objective was to evaluate the usefulness of procalcitonin and neopterin in distinguishing among aetiologies as well as severity in patients with pneumonia. PATIENTS: A total of one hundred sixteen patients with clinical, radiographic and microbiological diagnosis of pneumonia were grouped by aetiology, pneumonia severity index, and by the presence of unilobar or multilobar radiographic pulmonary infiltrates. Procalcitonin and neopterin were measured by immunoassays. RESULTS: Patients with pneumococcal pneumonia presented elevated procalcitonin and neopterin levels, being higher in bacteraemic than in non-bacteraemic pneumonia. Patients with Legionella pneumonia presented elevated neopterin levels and slightly elevated procalcitonin levels. Patients with tuberculosis and Pneumocystis jirovecii pneumonia presented elevated neopterin and low or not detectable procalcitonin. Procalcitonin and neopterin levels were increased in high-risk classes of pneumonia severity index. Both parameters yielded significant correlation to the radiographic extent and also to young age. CONCLUSIONS: Procalcitonin and neopterin levels vary depending on age, aetiology and severity of pneumonia. Together with clinical and microbiological data, combined measurement can help to identify patients who might benefit from additional therapies.

Adult↗
PubMed1999

Neopterin concentrations in fetal and maternal blood: a marker of cell-mediated immune activation.

OBJECTIVE: Neopterin is generated by macrophages and monocytes in response to cytokine and endotoxin stimulation and is a sensitive marker of the severity of infectious-, autoimmune-, and alloimmune-mediated inflammatory disorders. This study was designed to evaluate fetal and maternal neopterin concentrations during the second half of pregnancy. STUDY DESIGN: We conducted a cross-sectional analysis of serum neopterin values with a sensitive radioimmunoassay in 35 paired fetal and maternal and 8 neonatal samples. The fetal and maternal samples were obtained between 20 and 38 weeks' gestation at the time of diagnostic cordocentesis. All maternal, fetal, and neonatal samples were derived from uncomplicated pregnancies resulting in term delivery of appropriately grown fetuses. RESULTS: Fetal neopterin concentrations increased across gestation (r = 0.64, P <.001), and mean values were significantly higher than paired maternal values (6.28 [+/-2.44] ng/mL vs 2.05 [+/-0.87] ng/mL, P <.001]. In contrast, maternal neopterin concentrations did not correlate with gestational age (r = 0.22, P =.24). No significant correlation was found between fetal and maternal values (r = 0.34, P =.07). CONCLUSION: Fetal neopterin values rise significantly across gestation. They are substantially greater than maternal levels and are not correlated significantly with paired maternal levels. These findings are the first report of a physiologically normal range for fetal neopterin concentrations in a sample of uncomplicated pregnancies. The values suggest progressive increases in fetal cell-mediated immunity and macrophage-monocyte activation as gestation progresses.

Biomarkers↗
PubMed1997

Periodontitis and concentrations of the cellular immune activation marker neopterin in saliva and urine.

Neopterin concentrations in diverse body fluids provide a well established indication for activation of the cell-mediated immune system. Neopterin concentrations were measured in the saliva and urine of 29 patients with varying numbers of teeth affected by periodontitis. While neopterin concentrations in urine increased slightly but not significantly in parallel with increasing numbers of affected teeth, salivary neopterin levels showed a significant and positive correlation with number of diseased teeth (linear correlation coefficient = 0.48, P = 0.012). Additionally, when the patients were grouped according to the median number of affected teeth (20), salivary specimens of subjects with one to 20 affected teeth showed significantly lower neopterin concentrations than specimens from those with more than 20 diseased teeth (P = 0.0045, Student's t-test). In contrast, urinary neopterin concentrations did not differ significantly among these two groups. This pilot study suggests that salivary neopterin concentrations may reflect local immune activation even in situations where no systemic activation can be detected.

Adolescent↗
PubMed1998

Noninvasive monitoring using serum amyloid A and serum neopterin in cardiac transplantation.

The monitoring of allograft function for cardiac transplant patients still relies on endomyocardial routine biopsies. We investigated the diagnostic value of noninvasive monitoring using the parameters serum amyloid A protein and serum neopterin. The circulating levels of the acute phase reactant, amyloid A protein, and the macrophage product, neopterin, were measured serially in 13 patients after cardiac transplantation. The mean period of observation was 240 days. Nine acute cardiac allograft rejections, five cases of viral infection and eight cases of bacterial infection occurred. The levels of serum amyloid A protein and serum neopterin remained low (x = 6.0 mg/dL and 12.6 nmol/L, respectively) during the periods of stable graft function. In contrast, both parameters were significantly elevated (p < 0.01) during the rejection episodes (x = 12.7 mg/dL and 38.0 nmol/L for serum amyloid A protein and serum neopterin, respectively). For a reliable differentiation between rejection and stable graft function, serum amyloid A protein had a diagnostic accuracy of 84% (with a cut-off level of 10 mg/dL) and serum neopterin had one of 75% (with a cut-off level of 23 nmol/L). However, significant increases in the circulating levels of serum amyloid A protein and serum neopterin were also observed during bacterial (x = 14.9 and 88 nmol/L, respectively) and viral (x = 6.2 mg/dL and 44 nmol/L, respectively) infections. The detection of immunological complications after cardiac transplantation using serial measurements of serum amyloid A protein and serum neopterin is possible. These parameters can be used to help in judging both the need and the optimal timing for the otherwise frequent endomyocardial biopsies.

Antilymphocyte Serum↗
PubMed2003

Influence of neopterin on the generation of reactive oxygen species in human neutrophils.

Neopterin is synthesized by human monocyte-derived macrophages primarily upon stimulation with the cytokine interferon-gamma. We studied the influence of neopterin on the generation of reactive oxygen species (ROS) in human peripheral blood neutrophils. Radical formation was measured using a biochemiluminometer. Neutrophils were isolated from peripheral blood of healthy donors. The generation of ROS by neutrophils suspended in Earl's solution (pH=7.4) at 37 degrees C was investigated by monitoring of chemiluminescence using luminol and lucigenin as light emitters. Neopterin induced chemiluminescence in suspensions of neutrophils in the presence of luminol, but not of lucigenin. Neopterin affected only adhesive cells. Addition of neopterin into the suspension of the cells involving D-mannitol, L-histidine and diazabicyclo[2.2.2]octane (DABCO) decreased luminol-dependent chemiluminescence (LDCL) of the neutrophils. The action of superoxide dismutase (SOD) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) reduced neopterin-induced LDCL of neutrophils. Data suggest that neutrophils respond on exposure to neopterin with additional generation of singlet oxygen, hydroxyl radical and nitric oxide by nicotinamide adenine dinucleotide phosphate (NADPH)-independent pathways.

Cyclic N-Oxides↗
PubMed1998

Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells.

Numerous studies indicate that proinflammatory substances like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as macrophage-derived neopterin are increased in atherosclerotic tissue and thus are potentially involved in the process of atherogenesis. Since apoptotic death of vascular smooth muscle cells (VSMC) is reported to occur in atherosclerotic lesions, we investigated the effects of neopterin, TNF-alpha, and IFN-gamma on apoptosis in cultured VSMC. Morphological changes characteristic of apoptosis as well as DNA fragmentation were detected in cells treated with neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma. Simultaneously, neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma led to inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) synthesis. NO generation was significantly reduced when cells were cotreated with the competitive iNOS inhibitor aminoguanidine. This was accompanied by decreased percentual apoptosis as detected by FACS analysis using all kinds of stimuli. We conclude that neopterin as well as TNF-alpha/IFN-gamma are potent mediators of apoptotic death in VSMC which is at least in part triggered by NO synthesis induced by these proinflammatory mediators.

Animals↗
PubMed2000

Serum neopterin and complex stenosis morphology in patients with unstable angina.

OBJECTIVES: We sought to assess the relation between serum neopterin concentration and complex coronary artery stenosis in patients with unstable angina. BACKGROUND: Monocyte activation is associated with acute atheromatous plaque disruption and acute coronary syndromes. Angiographically demonstrated complex coronary stenosis is often an expression of plaque disruption. Increased serum concentration of neopterin, a pterydine derivative secreted by macrophages after stimulation by interferon-gamma, has been observed in patients with acute coronary syndromes as compared with control subjects and patients with stable angina pectoris. METHODS: We studied 50 patients with unstable angina (32 men) who underwent coronary angiography after hospital admission. All coronary stenoses with > or =30% diameter reduction were assessed and classified as "complex" (irregular or scalloped borders, ulceration or filling defects suggesting thrombi) or "smooth" (absence of complex features). Serum neopterin levels were assessed within 24 h of hospital admission using a commercially available immunoassay (enzyme-linked immunosorbent assay kit, IBL, Hamburg, Germany). RESULTS: Thirty-nine patients were classified in Braunwald class IIIb, four in class IIb and seven in class Ib. The number of complex lesions per patient was 2.6+/-1.8 (mean +/- SD). The mean neopterin concentration was 7.76+/-3.62 nmol/liter. A significant correlation was observed between neopterin serum concentration and the presence of complex coronary stenoses (r = 0.35, p = 0.015). Multiple regression analysis showed that serum neopterin (p < 0.0001) was independently associated with the number of complex lesions. Other variables associated with complex lesions were the number of vessels with > or =75% stenosis (p < 0.0001), plasma creatinine (p = 0.003), triglycerides (p = 0.014) and a history of unstable angina (p = 0.032). CONCLUSIONS: Serum neopterin concentration is associated with the presence of angiographically demonstrated complex lesions in patients with unstable angina and may represent a marker of coronary disease activity.

Aged↗
PubMed2001

Elevated serum levels of soluble interleukin-2 receptor, neopterin and beta-2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis.

BACKGROUND: It has not been assessed whether high levels of soluble interleukin 2 receptor (sIL-2R), neopterin and beta-2 microglobulin in idiopathic dilated cardiomyopathy reflect heart failure severity and/or an active autoimmune process. The aim of this study was to relate serum levels of these markers to clinical and autoimmune features. METHODS: We studied 60 patients with idiopathic dilated cardiomyopathy, 67 controls with ischemic heart failure and 34 normals. RESULTS: Abnormal levels of sIL-2R, but not of neopterin and beta-2 microglobulin, were more frequent in idiopathic dilated cardiomyopathy than in ischemic patients (35% vs. 16%; P=0.02) or in normals (35% vs. 12%, P=0.01); mean sIL-2R levels were, however, similar in idiopathic dilated cardiomyopathy and ischemic heart failure (842+/-75 vs. 762+/-93 U/ml, P=NS). In idiopathic dilated cardiomyopathy abnormal levels of sIL-2R were associated with lower peak oxygen consumption (P=0.008), higher neopterin and HLA class II expression in the myocardium (P=0.02), but were unrelated to cardiac autoantibody status or titer. In addition, abnormal levels of neopterin were associated with adverse prognosis and higher beta-2 microglobulin; abnormal levels of beta-2 microglobulin with lower echocardiographic percent fractional shortening, higher sIL-2R and higher neopterin. CONCLUSIONS: There is no convincing evidence that abnormal sIL-2R, neopterin and/or beta-2 microglobulin are disease-specific markers of idiopathic dilated cardiomyopathy. The lack of association with cardiac autoantibodies suggests that these abnormalities are mainly related to heart failure severity rather than autoimmune pathogenesis. In keeping with this view, high levels of sIL-2R, neopterin and/or beta-2 microglobulin identified a subset of idiopathic dilated cardiomyopathy patients with advanced disease and poor prognosis.

Adolescent↗
PubMed2002

Procalcitonin and neopterin as indicators of infection in critically ill patients.

BACKGROUND: : In critically ill patients, severe infection and systemic inflammation due to non-infectious causes produce very similar clinical presentations, and traditional infection markers do not always differentiate these two conditions. Both procalcitonin and neopterin have been suggested to aid in the early diagnosis of bacterial infections and in differentiating bacterial infections from systemic inflammatory, non-infectious diseases or from viral infections. METHODS: : Procalcitonin (PCT) and neopterin were analyzed in 208 ICU patients who developed acute fever or septic shock. Blood samples were taken every 8th h within 48 h of the onset of fever or septic shock. RESULTS: : A total 162/208 of patients had infection, the most common location being the respiratory tract. Mortality was higher in infected patients (31.4% vs. 10.9%; P < 0.01). The optimum cut-off levels in identifying patients with infection of daily peak PCT were 0.8 microg/L on day 1 and 0.9 microg/L on day 2, and both sensitivity (67.7% and 60.9%, respectively) and specificity (47.8% and 63%) were poor. Accordingly, the optimum cut-off values of peak neopterin were 18 and 16 pg/L. The sensitivity was 62.7% on day 1 and 69.3% on day 2, while specificity was correspondingly 78.3% and 67.9%. There were no significant differences between the markers in discriminating between patients with infection or inflammation. Both PCT and neopterin increased with the severity of infection. They were higher in non-survivors. CONCLUSION: : PCT and neopterin were equally effective, although not very accurate in differentiating between infection and inflammation in critically ill patients. Neopterin was more specific than PCT, suggesting that neopterin is related to the activity of inflammatory response.

Adult↗
PubMed1999

Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells.

Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of the cellular immune system. Concerning inflammatory disorders of the lung, e.g. sepsis or sarcoidosis, high serum neopterin levels have been reported to correlate well with the severity of the disease. These situations are often associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the potential effects of neopterin on ICAM-1 synthesis in the type II-like pneumocyte cell line L2. Detection of ICAM-1 gene expression by reverse transcriptase-polymerase chain reaction revealed a dose-dependent effect of neopterin, with maximum impact following 12-h incubations. Comparable results were obtained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neopterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibitor of NF-kappaB, the stimulating effects of neopterin on ICAM-1 gene expression and protein generation may be mediated by activation of this transcription factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolongation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium.

Animals↗
PubMed2004

Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

BACKGROUND: Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. OBJECTIVES: The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. METHODS: Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). RESULTS: Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. CONCLUSION: Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

Adjuvants, Immunologic↗