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PubMed1987

Neopterin as discriminating and prognostic parameter in healthy homosexuals, ARC and AIDS patients.

Urinary neopterin, a sensitive marker for activation of cell mediated immunity, is compared to clinical and laboratory data in 5 patients with AIDS, in 15 patients with ARC and in 40 male subjects without AIDS-related clinical signs attending an AIDS outpatient clinic. The sensitivity of neopterin for AIDS-related diseases was higher than that of the CD4+/CD8+ subset ratio. The differences in neopterin levels between the controls, ARC and AIDS patients were found to be more significant than the T-cell subset data. The observation that the 3 AIDS patients with the highest neopterin levels have died whereas the two others with the lower levels are still alive also underlines the prognostic potential of urinary neopterin level determinations. Measurement of urinary neopterin is thus recommended as an additional criterion for monitoring ARC and AIDS patients.

AIDS-Related Complex↗
PubMed1988

Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus-1.

We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Intrathecal production of neopterin in aseptic meningo-encephalitis and multiple sclerosis.

Neopterin levels in cerebrospinal fluid (CSF) and serum were measured with a sensitive radioimmunoassay in patients with multiple sclerosis (MS), aseptic meningo-encephalitis (AM), other mostly non-inflammatory neurological diseases, and controls with tension headache or psychoneurosis. Elevated levels of neopterin were found in CSF in most patients during acute phase of AM, and normalization after clinical recovery. The elevation in CSF was not reflected in serum. Only four of 24 MS patients--three of them examined during exacerbation--had slight elevation of neopterin in CSF and all had normal serum levels. Neopterin levels in CSF correlated with mononuclear cell count. The elevation of neopterin observed in CSF in inflammatory CNS diseases despite low cell numbers in CSF compared to blood might reflect a high activation level of cells locally in the CNS. Neopterin in CSF is a valuable marker of acute cellular immune response.

Adult↗
PubMed1983

Significance of urinary neopterine in gynecological oncology: follow-up of patients with ovarian cancer.

In patients with genital cancer (N = 108) significantly higher mean neopterine levels were found than in a healthy control group. Prior to therapy elevated neopterine levels were seen in 60% of the patients with cancer of the genitals varying between 90% (ovarian cancer) and 54% (cervical cancer). Nine patients with ovarian cancer (stages IIb-IV) were followed for a period of 16 months to date. All patients had elevated neopterine values prior to therapy. When the urinary neopterine excretion remained increased over the period of observation, progression of the tumor occurred within a few months. In patients with complete or partial remission of the tumor, the neopterine excretion dropped to normal values. Thus, we feel that neopterine sampling may be helpful in the follow-up of patients with ovarian cancer, as tumor progression is indicated very early, before clinicoroentgenological findings are present.

Adult↗
PubMed1994

[Serum neopterin, bacteremia and viral antibodies in dilated cardiomyopathy].

Quantitation of neopterin and morphological examination of bacteria circulating in the blood of 28 patients with dilated cardiomyopathy gave evidence for elevated neopterin concentrations in 22 of the examinees (> 10 nM/l). The highest neopterin levels occurred in patients with L-form bacteria. Concentrations of neopterin and antibodies to cytomegalovirus, herpes simplex were related. The above antibodies were associated with high neopterin levels in the serum. It is suggested that high amounts of serum neopterin may result from combination of viral and bacterial infection in dilated cardiomyopathy sufferers.

Adolescent↗
PubMedDate not supplied

Serum neopterin levels in haematological malignancies.

BACKGROUND: Neopterin is an intermediate in the pathway of pteridines released in vitro from non proliferating activated cells such as macrophages stimulated with interferons. Increased urinary excretion of neopterin has been described in conditions of cell-mediated immune activation and in neoplastic diseases, including haemopoietic tumours. METHODS: We studied by radioimmunoassay serum neopterin levels of 91 patients with haematological malignancies differing in diagnosis, stage, treatment, and disease duration. RESULTS: Mean patient neopterin (13.5 nmol/L) was increased compared to 69 healthy controls (5.4 nmol/L, P < 0.001), and individual levels were related to patient survival (P = 0.006). No relevant differences were found among the various disorders, whilst advanced stages and active diseases had higher levels than initial stages and non-active diseases. Furthermore, off-therapy patients in stable remission did not differ from normals. Among subjects on therapy, patients on alpha-interferon had a higher percentage of (dose-related) neopterin elevation, in spite of a steady disease. CONCLUSIONS: We suggest that serum neopterin dosage has prognostic value in staging and follow-up, and may provide a useful tool for monitoring the therapy (particularly with biological response modifiers) of haematological neoplasias.

Adult↗
PubMed1993

[Serum and urinary neopterin levels in sarcoidosis].

Serum and urinary neopterin levels were determined by high pressure liquid chromatography in 26 patients with pulmonary sarcoidosis and 12 healthy controls. Neopterin levels were significantly higher in sarcoidosis patients than in the controls. Neopterin levels differed from serum angiotensin converting enzyme (ACE) activities and were significantly higher in radiologic stage 1 and 2 than in radiologic stage 0 in patients not receiving prednisolone. No significant correlation was found between neopterin level and serum ACE activity. On the other hand, a significant correlation was found between neopterin level and serum adenosine deaminase activity. We believe that serum and urinary neopterin levels may be a more clinically valuable method of assessing pulmonary sarcoidosis than serum ACE activity.

Adult↗
PubMed1993

Urinary neopterin as a predictive marker of coronary artery abnormalities in Kawasaki syndrome.

We investigated whether urinary neopterin concentrations respond to the pathological conditions (especially coronary artery dilatation) of Kawasaki syndrome. All of 29 children with Kawasaki syndrome had very high urinary neopterin concentrations. Increased urinary neopterin concentrations coincided with fever and with monocytosis in peripheral blood. The urinary neopterin excretion peaking within the first 8 days after onset correlated with the development of coronary artery dilatation. Increased urinary neopterin concentrations indicate that cell-mediated immunity is activated in patients with Kawasaki syndrome. Endogenous interferon-gamma and activation of monocytes/macrophages may play a role in the pathogenesis of Kawasaki syndrome. Not only do neopterin concentrations correlate with symptoms in the acute phase of Kawasaki syndrome, they also act as a predictive marker of coronary artery abnormalities in affected patients.

Biomarkers↗
PubMed1993

The role of neopterin in assessing disease activity in Crohn's disease: classification and regression trees.

Neopterin, a product of human monocytes/macrophages stimulated by gamma-interferon, was previously found to be correlated with clinical activity of Crohn's disease. The present investigation attempted to identify more precisely the role of neopterin for assessment of clinical activity in a multivariate setting. A broad panel of clinical and laboratory variables was obtained on 76 patients. Neopterin was determined in urine by high performance liquid chromatography. Using a 4-point clinical activity score as dependent variable, multivariate linear discriminant analyses were performed in order to identify subsets of statistically independent laboratory activity indices. Neopterin was shown to be an independent indicator for clinical activity. The significant variables were then tested together with the eight constituent variables of the Crohn's Disease Activity Index. The resulting model, which consisted of the three laboratory variables--erythrocyte sedimentation rate, serum protein and neopterin, together with pain score--was further subjected to two multivariate techniques for comparison: polychotomous logistic regression analysis and the technique of classification and regression trees. By all methods, neopterin was included into the multivariate models, confirming that its determination aids in the assessment of clinical activity in Crohn's disease.

Adult↗
PubMedDate not supplied

Correlation between pretreatment serum levels of neopterin and response to interleukin-2 immunotherapy in cancer patients.

IL-6 levels have been proven to correlate with resistance to IL-2 immunotherapy. Since IL-6 may be produced by both macrophages and TH2 lymphocytes, it is not possible to establish whether the negative prognostic significance of IL-6 levels may primarily depend on an enhanced macrophage or TH2 activation. Macrophage activation may be documented by the increase in its specific marker neopterin. In an attempt to establish whether the negative significance of IL-6 high levels prior to IL-2 immunotherapy may reflect an enhanced macrophage activation, we have investigated the relation existing between pretreatment concentrations of neopterin and response to IL-2 immunotherapy in cancer patients. The study included 20 metastatic renal cell cancer patients, who were treated with IL-2 subcutaneously at 6 million IU/day for 5 days/week for 6 weeks. Before the onset of IL-2 therapy, abnormally high serum levels of neopterin were seen in 11/20 patients. Moreover, neopterin concentrations were significantly correlated with those of IL-6. Tumor regression rate was significantly higher in patients with normal than in those with elevated levels of neopterin prior to therapy (5/9 vs 1/11, P < 0.05), as well as the percent of the survival at 1 year (9/9 vs 4/11, P < 0.01). This preliminary study would suggest that pretreatment values of the macrophage marker neopterin correlate with resistance to IL-2 cancer immunotherapy.

Adult↗
PubMedDate not supplied

Relation between macrophage and T helper-2 lymphocyte functions in human neoplasms: neopterin, interleukin-10 and interleukin-6 blood levels in early or advanced solid tumors.

At present, it is known that there are two main mechanisms responsible for cancer-related immunosuppression, mediated by macrophages and by TH2 lymphocytes. The relation existing between macrophage- and TH2-mediated immunosuppression still remains to be understood. The present study was performed in an attempt to establish which is the correlation existing in cancer patients between IL-10 and neopterin levels, which reflect TH2- and macrophage-mediated suppressive events, respectively. The study included 40 solid tumor patients and 60 healthy subjects as controls. Serum concentrations of neopterin and IL-10 were measured by the RIA method and by an immuno-enzymetric assay, respectively. Because of its possible production both by TH2 and macrophages, serum levels of IL-6 were also determined. Neopterin, IL-10 IL-6 mean concentrations were significantly higher in cancer patients than in controls. Mean values of both neopterin and IL-6 were significantly higher in metastatic patients than in those with locally limited disease. IL-10 mean levels were also significantly higher in patients with metastatic disease. IL-6 levels were significantly correlated with those of neopterin, whereas no correlation was found between neopterin and IL-10 values. This preliminary study would suggest that macrophage- and TH2-mediated immunosuppression may occur independently in solid tumors, and that it becomes more evident with disease progression.

Adult↗
PubMedDate not supplied

Increased concentrations of neopterin in plasma, ascites and ovarian cyst fluid in malignant tumours compared with benign ovarian tumours.

Neopterin is a marker of the activation of cell-mediated immunity. The aim was to determine whether the concentrations of neopterin differ in plasma, ascites and ovarian cyst fluid between patients with ovarian cancer and patients with benign ovarian tumours. Neopterin was measured in 29 patients with cystic ovarian tumours of unknown histology. 14 ovarian cancers and 15 benign ovarian tumours were diagnosed histologically. Patient age and tumour size did not differ significantly between the groups. Neopterin levels were determined in plasma, and in ascites and cyst fluid by ELISA. The neopterin concentration in plasma, ascites and ovarian cyst fluid was significantly higher in patients with ovarian cancer compared with patients with benign ovarian tumours of the same size. The study shows that activation of cell-mediated immunity, defined as increased formation of neopterin, was increased in patients with ovarian cancer compared with patients with benign ovarian tumours.

Aged↗
PubMed1998

Neopterin as a prognostic parameter in patients with squamous-cell carcinomas of the oral cavity.

Concentrations of neopterin, which is produced by human monocytes/macrophages upon stimulation by interferon-gamma, were measured in urine specimens in 23 patients with squamous-cell carcinoma of the oral cavity at diagnosis and in 12 treated patients with the same disease when recurrence of the tumor was recognized. Tumor histology and routine laboratory parameters were concomitantly determined. Urinary neopterin values showed no statistically significant correlation with tumor differentiation, tumor size or patient age, but they were significantly higher in patients with a recurrent tumor. Patients were followed for up to 4 years, and the ability of all variables to predict fatal outcome was assessed. In univariate analysis, only neopterin (p = 0.01) and the variable recurrent vs. first-diagnosed tumor were significant predictors of survival. In multivariate analysis, a combination of neopterin (p < 0.01) and the variable recurrent vs. first-diagnosed tumor (p = 0.06) was found to jointly predict survival. Thus, urinary neopterin concentrations provide valuable prognostic information in patients with squamous-cell carcinoma of the oral cavity.

Adolescent↗
PubMed1990

Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.

We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.

AIDS Dementia Complex↗
PubMed2004

A new HPLC method for serum neopterin measurement and relationships with plasma thiols levels in healthy subjects.

Neopterin, a pyrazinopyrimidine compound, serves as a marker of cellular immune system activation, and it can be used as a prognostic predictor for certain types of diseases. We propose a new simple HPLC method to measure serum neopterin with highly sensitive fluorimetric detection. After TCA serum protein precipitation, the supernatant was diluted five times, injected into a C18 reversed-phase column and eluted at a flow rate of 1.5 mL/min by an isocratic water-acetonitrile (99:1) mobile phase. The natural fluorescence of the molecule was detected at excitation wavelength 353 nm and emission 438 nm. In these conditions the neopterin retention time was about 4 min. Our proposed method was compared with a validated chromatographic separation, and the obtained data of the serum neopterin from 35 healthy volunteers were analysed by Passing-Bablok regression and Bland-Altman test. Neopterin measurement in healthy subjects was also employed to investigate on its potential relationships with plasma thiols levels.

Adult↗
PubMed1993

Neopterin levels in plasma during a longitudinal study in an area endemic for malaria.

Neopterin levels in plasma were measured during a longitudinal study of 75 patients living in an area endemic for malaria. The maximum levels were observed in August/September, the period of peak transmission of the disease. During the dry season, levels remain elevated. No relationship was found between the level of neopterin and the individual's immune status against malaria. Tumor necrosis factor (TNF), activated T lymphocytes subpopulations, soluble interleukin 2 receptors, and anti-circumsporozoite protein antibodies were not correlated with neopterin levels during the period of peak transmission. In contrast, neopterin levels were correlated with anti-Plasmodium falciparum antibodies detected by immunofluorescence. It was concluded that, in a population of chronic parasite carriers subjected to repeated infestations, neopterin was a good indicator of slowly acquired immunity in stable transmission area, but it poorly reflected acute immune responses.

Adolescent↗
PubMed2006

Use of neopterin as a bone marrow hematopoietic and stromal cell growth factor in tissue-engineered devices.

The in vitro response of early haematopoietic progenitors or stem cells (CD34+)--common for myeloid (granulocyte, eosinophil, megakaryocyte) and marrow stromal cell lineages, to neopterin, exogenously added to the liquid mouse bone marrow cultures, at doses 12.5-25 microg/ml culture medium, has been studied. The results obtained show a significant stimulation of common--myeloid and stromal/ mesenchymal progenitor cell proliferation and differentiation, as early as 24h to the 96h after the in vitro treatment with neopterin. On day 4 of cultivation the granulocyte/macrophageal proliferation and differentiation has been attenuated giving place to the marrow stromal/mesenchymal cell growth and differentiation. A functional role of neopterin as hematopoietic growth factor--essential for the proliferation and differentiation of bone marrow common (hematopoietic and stromal) progenitors is not yet clear and remains to be elucidated. The in vitro and ex vivo applying of neopterin--alone or in specific combinations with other cytokines (e.g. FGF-2) for the induction of marrow stromal/mesenchymal cell proliferation and differentiation, merits further investigations with regards to its future use in regenerative medicine. The results provide a theoretical basis for the application of neopterin in tissue-engineered devices: incorporated into biodegradable polymer microparticles (with encapsulated early bone marrow progenitors and other special supplements), it could be experimentally applied for fast and easy induction of endothelial, osteoblastic/osteogenic, neuronal and other cell lineage differentiation as well as for improving tissue trophical processes and reparative microenvironment.

Animals↗
PubMed1992

Neopterin concentrations in serum and cerebrospinal fluid in HTLV-I infected individuals.

The concentration of neopterin was measured in serum samples taken from individuals infected with HTLV-I: 5 from asymptomatic individuals, 1 from a patient with adult T-cell leukaemia and 30 from patients with tropical spastic paraparesis (TSP). In addition, cerebrospinal fluid (CSF) was available from 22 of the TSP patients and neopterin concentrations were determined in these. Elevated levels of neopterin were found in only 3 of the 36 HTLV-I-positive serum samples, all from TSP patients, but significantly elevated neopterin levels were observed in 12 of the 22 CSF samples. The localisation of the elevated neopterin concentrations to the CSF of patients with TSP suggests a marked degree of activation of the cell-mediated immune system intrathecally. This provides further evidence in favour of powerful immune mechanisms operating centrally in the pathogenesis of TSP.

Biopterins↗