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PubMedDate not supplied

Serum neopterin levels in liver cirrhosis.

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.

Adult↗
PubMed1988

Relationship between serum neopterin and lymphocytic alveolitis in sarcoidosis.

We have previously found elevated levels of serum (S-) neopterin in patients with active sarcoidosis. In the present study we therefore investigated the relationship between elevated S-neopterin and sarcoid alveolitis as reflected in bronchoalveolar (BAL) findings. Patients with elevated percentages of BAL-lymphocytes (n = 19) had significantly higher (p less than 0.01) S-neopterin levels (median 12.1 nmol/L) than those (n = 11) with normal percentages (median 8.5 nmol/L). Of 19 patients with elevated lymphocyte percentage 18 had increased S-neopterin. There was a significant correlation between S-neopterin levels and the concentration (p less than 0.01) as well as the percentage (p less than 0.05) of BAL-lymphocytes. On the other hand, no correlation was found between S-neopterin and the BAL-albumin/S-albumin ratios, the concentration of macrophages or the concentration of angiotensin converting enzyme in the BAL fluid. The results indicate a close relationship between S-neopterin and lymphocytic alveolitis in sarcoidosis. Furthermore, a possible relationship between elevated S-neopterin and the ratios of T helper to T cytotoxic-suppressor cells (TH/TC-S) in blood, assumed to reflect changes of the ratios in alveolitis, was examined. However, 34 of 37 sarcoid patients had TH/TC-S ratios within the normal range. The ratios of patients with normal and elevated S-neopterin did not differ.

Adult↗
PubMedDate not supplied

Serum neopterin levels in lung and breast cancer patients undergoing radiotherapy and/or chemotherapy.

The elevated neopterin levels observed in numerous haemotological diseases and parenchymatous malignomas suggested neopterin might be useful as a tumor marker. In a group of 60 patients suffering from advanced lung (18) or breast (42) cancer, serial determinations of serum neopterin were made before, during and after radiation and/or chemotherapy, during an observation period of 18 months, to check the potential value of neopterin in the therapeutic management of these tumor types. The neopterin profiles were compared with the clinical course and analysed with regard to response to therapy. Numbers of pathologically elevated serum neopterin levels were low. In only few cases was any agreement detected between changes in neopterin levels and therapeutic effects. Even chemotherapeutically induced depression in white blood counts generally did not increase serum neopterin levels. Thus the clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.

Biomarkers, Tumor↗
PubMed2006

Elevated neopterin levels in non-allergic asthma.

Neopterin is synthesized by human monocyte-derived macrophages upon stimulation with interferon-gamma (IFN-gamma). Measurement of neopterin concentration is useful to monitor cell-mediated (Th1-type) immune activation. In this study, we aimed to analyze the behaviour of neopterin in long lasting asthma considering its role as a marker of the Th1 environment and to establish the distinction between patients belonging either to the allergic or the non-allergic population, particularly in the elderly where asthma is often under diagnosed. Therefore we evaluated allergic parameters such as skin prick tests, IgE and hemogram (eosinophils count), and we compared our findings with neopterin values found in an age-matched control population. A group of individuals older than 65 was selected. It included 64 asthmatic patients (mean age 72+/-5 years) and 41 healthy individuals (mean age 79+/-7 years). In our study population, 42 patients presented positive skin tests, mainly to house dust mites. All patients were clinically stable and presented an average percentage of predicted forced expiratory volume in the first second (FEV1) of 73.6+/-25.3 and predicted median expiratory flow percentage (MEF50) of 38.8+/-26.7. Blood cell counts showed statistically different mean values of eosinophils between allergic and non-allergic controls (5.42+/-4.7% versus 2.8+/-2.8%; p<0.04). IgE values were increased in allergic asthmatic patients when compared with non-allergic asthmatic patients (493.2+/-549.8IU/ml versus 85.3+/-194.4IU/ml; p=0.000). Allergic asthmatic patients presented mean neopterin levels similar to those found in the control group (2.4+/-2.8ng/ml versus 2.1+/-1.9ng/ml). In contrast, in non-allergic asthmatic patients these values were higher when compared with the control group (4.0+/-4.7ng/ml versus 2.1+/-1.9ng/ml). Neopterin levels were lower in allergic asthmatic patients when compared with non-allergic asthmatic patients (2.4+/-2.8ng/ml versus 4.0+/-4.7ng/ml). Within asthmatic patients, those with higher neopterin values (>2.1ng/ml) presented lower mean IgE values (IgE</=336.58IU) than those with lower neopterin values (</=2.1ng/ml) who presented mean IgE values of 402.70IU. Our initial findings may lead to a better understanding of the immunoinflammatory pathways in asthma. Further studies will probably show that serum neopterin could became a useful marker for asthma classification including in elderly patients with long lasting disease.

Journal Article↗
PubMed1995

Serum neopterin level predicts HIV-related mortality but not progression to AIDS or development of neurological disease in gay men and parenteral drug users.

OBJECTIVE: To investigate the ability of elevated serum neopterin levels to predict independently mortality, progression to acquired immunodeficiency syndrome, and development of neurological disease. DESIGN: Cross-sectional and longitudinal study of gay and/or bisexual men and parenteral drug users. SETTING AND PATIENTS: Patients included human immunodeficiency virus (HIV)-negative and -positive gay and/or bisexual men and parenteral drug-using men and women who volunteered for an outpatient study of the natural history of HIV infection. RESULTS: Serum neopterin levels were significantly elevated in HIV-positive patients (mean, 18.0 nmol/L; SD, 19.2 nmol/L), compared with those in HIV-negative patients (mean, 7.5 nmol/L; SD, 5.5 nmol/L) (P < .001). No differences in the serum neopterin levels could be detected between gay men and parenteral drug users. In HIV-positive patients, women had a higher serum neopterin level than did men (P = .03). The elevated serum neopterin levels were associated with an advanced clinical stage of HIV infection. After adjusting for the CD4 lymphocyte count and other potential confounders, the serum neopterin level was a significant independent predictor of mortality. The elevated serum neopterin levels did not predict progression to acquired immunodeficiency syndrome or development of clinically significant neurological disease. CONCLUSION: An elevated serum neopterin level predicts mortality, but it does not predict progression to acquired immunodeficiency syndrome or development of neurological disease among HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Serum neopterin in chronic beryllium disease.

We evaluated serum neopterin as a biomarker of chronic beryllium disease (CBD), for use in conjunction with the beryllium lymphocyte proliferation test (BeLPT) in workplace screening. Serum neopterin levels were determined by radioimmunoassay, and we compared levels in three groups: CBD (n = 86), beryllium sensitized (BeS) (n = 22), and normal (Nor) (n = 20). Those in the diseased group underwent pulmonary function tests, bronchoalveolar lavage (BAL), and maximal exercise testing. We correlated neopterin levels with results of these clinical parameters of disease severity. To evaluate the optimum sensitivity, specificity, and neopterin cut-off value, receiver operator characteristic (ROC) curves were generated. The median serum neopterin level in CBD was significantly higher than in BeS or in Nor [median 1.45, 25th, 75th percentiles (1.00, 2.7) ng/ml, 0.82 (0.67, 1.16) ng/ml, and 0.92 (0.86, 1.16) ng/ml, respectively] (P < 0.05). In CBD, we observed statistically significant associations between neopterin and measures of gas exchange and BAL cellularity. Using a neopterin value of 1.27 ng/ml, test specificity is 88%. In those workers with an abnormal BeLPT, serum neopterin has high positive predictive value (92%), and can identify disease, helping to distinguish it from BeS without the risks of biopsy.

Adult↗
PubMed1989

Prognostic relevance of urinary neopterin in non-Hodgkin's lymphomas.

Neopterin excretion levels were assessed in 66 consecutive patients affected by non-Hodgkin's lymphomas (NHL). The logarithm of the mean value of the whole series was 2.71 (log [mumol neopterin/mol creatinine]), significantly higher (P less than 0.001) than the control value (2.12). Fifty-six of 66 patients had a raised excretion of neopterin in amounts statistically related to the stage of disease. The mean value (2.51) of patients in Stages I-II was lower than the mean value (2.86) of patients in Stage III-IV (P less than 0.001). The 2-year probability of survival was 64% for patients in Stages I-II and 34% for patients in Stages III-IV. However, patients with lower neopterin excretion (less than 2.65) fared better than patients with higher neopterin excretion, regardless of the stage. Longitudinal analysis showed a trend toward a correlation between response to therapy and neopterin excretion. In NHL, the raised neopterin excretion appears to be a consequence of activation of the host immune system rather than a product of the malignant cells. But this excessive activation of the monocytes-macrophages, as reflected by urinary neopterin levels, is not accompanied by a better outcome. In conclusion, although neopterin cannot be considered a typical tumor marker, nevertheless it is an useful prognostic marker in NHL.

Biopterins↗
PubMed2001

Inverse relationship between neopterin and immunoglobulin E.

Polarized human T helper (Th) cells play a key role in the network of the specific immune system compartments. Cell-mediated immune response depends on activation of Th1-type cells, typically producing and releasing interferon-gamma and interleukin-2, whereas activation of Th2-type cells and production of cytokines such as interleukin-4, -5, and -10 are involved in humoral immune response and the production of immunoglobulins. Increased amounts of neopterin are produced during the Th1-type immune response by human monocytes/macrophages upon stimulation with the Th1-derived cytokine interferon-gamma, and thus the determination of neopterin concentrations allows us to monitor Th1-type immune response. We compared serum concentrations of neopterin with immunoglobulin E (IgE), a typical product of the Th2-type immune response, in order to examine the relationship between Th1-type and Th2-type immune system stimulation in 709 healthy outpatients, who visited the physician's office for a medical health checkup. Eleven percent presented with serum neopterin concentrations >8.7 nmol/L; 26% had increased serum concentrations of IgE (>100 kIU/L). There existed an inverse correlation between serum neopterin and IgE concentrations (Spearman's rank correlation coefficient: r(s) = -0.100; P < 0.01) which was stronger when excluding data < or = 8.7 nmol/L neopterin and < or = 100 kIU/L IgE (n = 246; r(s) = -0.519; P < 0.0001). Data indicate that increased serum neopterin concentrations are associated with low serum IgE and increased serum IgE with low serum neopterin concentrations. This finding fully agrees with the current understanding that in humans the activation of Th1 and Th2 cell-mediated immune responses are down-regulating each other.

Adolescent↗
PubMed2001

Admission neopterin and interleukin 12 concentrations in identifying infections in adult cancer patients.

Differential diagnosis between infections and neoplastic fever is a common diagnostic problem. The utility of admission serum concentrations of neopterin and interleukin 12 (IL-12) was prospectively evaluated in this respect. The infection group (n=56) had a higher median neopterin value (12.8 nmol/l vs 4.0 nmol/l, P<0.001) and neopterin-to-IL-12 ratio (1.74 vs 0.11, P<0.001) than the non-infection group (n=36); the median IL-12 values were higher in the latter group (10.6 pg/ml vs 71.6 pg/ml, P=0.007). According to the area under the operating characteristics curves (AUC), especially neopterin (0.90), but also the neopterin-to-IL-12 ratio (0.79), was good at identifying bacteremia. However, in differentiating infections in general from neoplastic fever (n=10), the neopterin-to-IL-12 ratio was less powerful (0.64), though still better than neopterin (0.58) and clearly better than IL-12 (0.42). The present results show that the neopterin-to-IL-12 ratio, which reflects simultaneously both the ongoing infection and the tumour load, may have promising clinical implications for differential diagnosis between infections and neoplastic fever.

Adult↗
PubMed1990

Value of urinary neopterin in the differential diagnosis of bacterial and viral infections.

Neopterin is released by stimulated macrophages. In this study we analyzed the diagnostic potential of urinary neopterin concentrations in patients with bacterial and viral infection. All but one of 17 patients with viral infection had increased urinary neopterin concentrations. Patients with bacterial urinary tract infection also showed increased neopterin concentrations, whereas patients with bacterial pneumonia had significantly lower neopterin levels. In addition, patients with acute bacterial pneumonia had lower neopterin levels than patients with protracted infection. A significant inverse correlation between urinary neopterin and hemoglobin concentrations was found. Neopterin concentrations could serve as a helpful additional marker of infectious diseases. Combined with other clinical and laboratory parameters it is a useful parameter for distinguishing between viral and bacterial origins of infection, as was shown by multivariate stepwise linear discriminant analysis.

Adult↗
PubMed1986

Neopterin in AIDs, other immunodeficiencies, and bacterial and viral infections.

An increase in total urinary neopterin was observed in 12 of 13 patients with acquired immunodeficiency syndrome (AIDS), seven of 13 patients with lymphadenopathy, one of six healthy homosexual males, seven of ten adult patients with staphylococcal pneumonia, 11 of 12 children with viral infections, four of seven children with bacterial infections, and 12 of 13 children with various immune defects. Extremely high values of total urinary neopterin and monapterin were observed in severely ill patients with AIDS and those with familial hemophagocytic lymphohistiocytosis. Neopterin excretion was normal in two AIDS patients with Kaposi's sarcoma, but without opportunistic infections at that time. On reexamination of one of these patients later on, elevated neopterin values were noted. Parallel increases in neopterin and monapterin were found, whereas biopterin was usually normal. The increase in total neopterin was mainly due to 7,8-dihydroneopterin and was accompanied by an increase in 3'-hydroxysepiapterin. Increased neopterin in urine is assumed to reflect the increase in GTP pool and GTP cyclohydrolase I activity as observed in stimulated monocytes. Thus, neopterin, as a measure of the activation of the nonspecific cellular immune system, may be used diagnostically to detect allograft rejection after transplantations and to follow-up HTLV-III positive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Neopterin levels and pulmonary tuberculosis in infants.

Neopterin is produced and released by human macrophages in response to stimulation with interferon-gamma and changes in neopterin concentrations indicate cellular immune activation. Pulmonary infection with Mycobacterium tuberculosis is also associated with increased neopterin levels in body fluids. We report the clinical course, the diagnostic results, and the urinary neopterin levels of seven children (ages 10 months-6(6/12) years) with pulmonary tuberculosis. Two of them had progressive primary tuberculosis, in one case caused by isoniazid resistance. Diagnostic criteria included chest radiographs, intradermal tuberculosis skin testing, and culture of aspirated secretions for tuberculosis. Neopterin levels were determined by high performance liquid chromatography. The five patients with uncomplicated primary disease and a good response to therapy with isoniazid, rifampin, and pyrazinamide showed no or slightly elevated neopterin levels (mean, 458 micromol/mol creatinine). In the two patients with progressive primary tuberculosis we documented excessively high neopterin levels (mean, 2170 micromol/mol creatinine). We conclude that neopterin may be a useful parameter for measuring the degree of disease activity and the response to therapy.

Antitubercular Agents↗
PubMed2003

Potential role of immune system activation-associated production of neopterin derivatives in humans.

Neopterin derivatives are produced by human monocyte-derived macrophages and dendritic cells upon stimulation with interferons. Neopterin concentrations measured in urine or blood reflect activation of cellular immunity and endogenous release of interferon-gamma. This review focuses on the clinical utility of measuring neopterin levels in inflammatory disease and the potential functions of neopterin as a mediator and/or modulator in the course of inflammatory and infectious processes. In vitro-studies revealed that neopterin derivatives exhibit distinct biochemical effects, most likely via interactions with reactive oxygen or nitrogen intermediates, thereby affecting the cellular redox state. Data support the hypothesis that the release of neopterin enhances the cytotoxic potential of activated macrophages and dendritic cells. In vivo, a strong correlation between neopterin levels and the severity, progression, and outcome of infectious and inflammatory diseases was found. The influence of neopterin derivatives on the cellular metabolism may provide an explanation for these clinical observations.

Cell Line↗
PubMed2003

Neopterin production in posttraumatic stress disorder before and after pharmacotherapy.

Post-traumatic stress disorder (PTSD) has been associated with decreased neopterin levels. In the present study, we evaluated whether this low neopterin levels would normalize following pharmacotherapy with sertraline in PTSD. Fourteen patients with PTSD and 14 controls were enrolled in the study. A clinical evaluation and measurements of neopterin levels before and after sertraline treatment were performed. In addition, all patients were assessed with the Clinician Administered PTSD Scale (CAPS). The mean neopterin levels were significantly lower in the patient group than control group at baseline and were negatively correlated with the duration of illness, or severity of illness. Sertraline treatment decreased the symptoms of PTSD; however this was not accompanied by a significant increase in neopterin production. In conclusion, our results reveal that the failure for neopterin to normalize through symptom alleviation suggests that either neopterin may be a trait marker of the illness, or that more sustained treatment is necessary to elevate the neopterin production.

Adolescent↗
PubMed1981

Urinary neopterine as marker for haematological neoplasias.

Urinary neopterine levels were studied in 79 normal subjects and in 112 patients with haematological neoplasias. The mean values in 79 patients with active disease were significantly raised compared to the control group. Results obtained in 79 patients with active disease indicate that 91% had neopterine levels higher than the mean value of 79 normal individuals +3 SD. There is only a little overlap between the range of neopterine levels in cancer patients and the range in healthy subjects. No significant difference was found between the mean urinary neopterine levels of 33 patients with non-Hodgkin's or with Hodgkin's lymphoma in remission and the healthy group. Only 15% of these patients had elevated neopterine levels. The mean urinary neopterine levels correlated well with the tumor stage in patients with chronic lymphocytic leukaemia and with non-Hodgkin's disease. In patients with chronic leukaemia those without hepatosplenomegaly excreted significantly more neopterine than controls, and patients with hepatosplenomegaly significantly more than those without hepatosplenomegaly. It is concluded that urinary neopterine levels are of value for following the progression of haematological neoplasias.

Adolescent↗
PubMed1985

Neopterin release in human mixed lymphocyte culture: requirement of HLA-DR disparity.

Recent evidence suggests that immune responses in vivo as well as in vitro are accompanied by release of neopterin [C. H. Huber, et al. (1983) J. Immunol. 130, 1047]. This investigation aimed to elucidate the genetic control of in vitro neopterin release in family mixed lymphocyte culture (MLC) studies. Neopterin levels and responder cell proliferation were assessed in a total of 92 MLCs established from different intrafamilial combinations. Results indicated a strong association between the magnitude of responder cell proliferation and the neopterin levels induced by stimulation with allogeneic cells. This conclusion was based on three findings: first, almost no neopterin release and proliferation was seen in MLCs established between HLA genotypically identical siblings; secondly, very low proliferation and neopterin levels were observed in MLCs between HLA-DR phenotypically identical family members; and thirdly, high neopterin release and strong cellular proliferation were a feature of MLCs established between individuals differing for at least one HLA-DR antigen. We thus conclude that T cell activation subsequent to recognition of HLA-DR disparity represents an essential prerequisite for induction of neopterin release in human MLC.

Biopterins↗
PubMed1992

Neopterin plasma levels in burn patients.

Burn victims have severely depressed cellular immunity and despite careful hygiene, antibiotics and early surgical therapy the infection rate remains high. The assessment of plasma neopterin levels can be considered as an indirect measurement of macrophage function, because activation of macrophages is accompanied by the release of D-erythro-neopterin. The influence of burn trauma on neopterin levels was investigated to determine whether neopterin estimations might have a prognostic or diagnostic value. Twenty patients with a mean age of 36 +/- 16 years and a TBSA of 45.5 per cent +/- 23 were studied. During the whole hospital treatment daily blood samples were analysed for neopterin levels using radioimmunoassay. Starting from normal levels (9 +/- 1.6 nmol/l), neopterin content increased continuously until day 10 (30-40 nmol/l), then fluctuated around these high levels for several weeks. There were no differences between patients with TBSA less than 35 per cent or greater than 35 per cent, and between survivors and non-survivors. Burn injury caused a constant increase of plasma neopterin indicating an intact reaction by macrophages. It can be used as an additional parameter for the diagnosis of sepsis: high values being a sign of adequate reaction by macrophages, whereas low neopterin values in the presence of bacteraemia and clinical symptoms of sepsis show a deleterious impairment of immune functions.

Adult↗
PubMed2005

Serum neopterin for early assessment of severity of severe acute respiratory syndrome.

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.

Adrenal Cortex Hormones↗