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PubMedDate not supplied

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.

Adult↗
PubMed1994

Changes in serum neopterin and serum beta 2-microglobulin in subjects with lung infections.

Our aim was to investigate whether serum neopterin and beta 2-microglobulin have any value in the distinction between Pneumocystis carinii pneumonia (PCP) and pneumonia due to extracellular bacteria. Also, to study whether neopterin and beta 2-microglobulin would correlate with the clinical course of lung infections in human immunodeficiency virus (HIV)-positive and HIV-negative patients. Thirty HIV-positive subjects with PCP, 9 HIV-positive patients with bacterial pneumonia, and 16 HIV-negative patients with bacterial pneumonia were investigated. Thirty eight asymptomatic HIV-positive subjects and 48 healthy blood donors were used as controls. The HIV-positive patients with PCP and the HIV-positive subjects with bacterial pneumonia had significantly and similarly elevated levels of neopterin and beta 2-microglobulin in the acute stage. In the weeks before the acute stage of PCP, neopterin and beta 2-microglobulin had been increasing. After start of treatment, serum neopterin declined significantly, whilst serum beta 2-microglobulin remained elevated. The HIV-negative patients with bacterial pneumonia had significantly increased serum concentrations of both markers in the acute stage, and had decreasing serum concentrations in the weeks after treatment. We conclude that neither neopterin nor beta 2-microglobulin seem to be of value in distinction between PCP and bacterial pneumonia in HIV-positive subjects. In the HIV-positive patients, neopterin may correlate partly with the clinical activity of PCP, whilst serum beta 2-microglobulin may remain elevated after PCP, despite treatment and recovery. The elevated level may, in part, be due to repeated infections and progression to acquired immune deficiency syndrome (AIDS).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1991

Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease.

We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.

Biopterins↗
PubMed1996

Intrathecal production of neopterin and beta 2 microglobulin in tick-borne encephalitis (TBE) compared to meningoencephalitis of other etiology.

To study the pathophysiology of tick-borne encephalitis (TBE), the kinetics of neopterin and beta 2 microglobulin (beta 2M) production were measured in sequential, cerebrospinal fluid (CSF) and serum samples in 133 patients with aseptic meningoencephalitis (TBE, n = 72; non-TBE, n = 61). Intrathecal production of neopterin was demonstrable in all patients. Neopterin levels in CSF were elevated already at day 2: geometric mean value in TBE 36 nmol/l (range 1-253), in the non-TBE group 29 nmol/l (0.2-96). At day 9 and week 6 the neopterin level was significantly higher in TBE (86 (19-725) and 17 (4-122) nmol/l) than in non-TBE (28 (5-109) and 3 (0.2-58) nmol/l) (p < 0.001). After 1 year CSF levels were within the normal range. The beta 2M response in CSF followed the pattern of neopterin. The intensity and duration of neopterin and beta 2M was not correlated to the clinical course. Neopterin seems to be a more sensitive indicator of intrathecal T-cell response and inflammatory reaction than beta 2M. The results indicate that a long-lasting strong inflammatory reaction is of pathophysiological significance in TBE.

Adolescent↗
PubMed1993

Cerebrospinal fluid neopterin levels in children with central nervous system leukemia.

Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high-grade lymphomas). When meningeal relapse was diagnosed, all patients had CSF neopterin levels higher than mean normal value +2 standard deviations. No significant correlation between the blast count in the CSF and neopterin levels was observed. CSF data before relapse were available in 10 children: the neopterin values at relapse were significantly higher than values observed at diagnosis. In 3 patients, elevated neopterin levels preceded the occurrence of neurologic signs and the detection of blast cells in CSF by 15 to 30 days. In the absence of infection, the rise of CSF neopterin levels in patients with hematologic malignancies indicates an active phase of the disease. This could reflect a cell-mediated immunologic process induced by malignant cells. The measurement of CSF neopterin should be helpful in the monitoring of patients to detect early meningeal relapse.

Adolescent↗
PubMed2002

Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies.

OBJECTIVE: We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs). METHODS: Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained. RESULTS: Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R(2) =0.40-0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48). CONCLUSIONS: Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.

Adolescent↗
PubMed2002

Monocyte-derived dendritic cells release neopterin.

Increased neopterin concentrations in body fluids are found in diseases associated with activated, cell-mediated immunity including infections, autoimmune diseases, and certain malignancies. Monocytes/macrophages are known to secrete large amounts of neopterin upon stimulation with interferon-gamma (IFN-gamma). Ontogenetically, the major part of dendritic cells (DC) belongs to the myeloid lineage. Therefore, we investigated whether cultured monocyte-derived DC can elaborate neopterin. Cells were treated with cytokines in the presence or absence of monocyte-conditioned medium as a maturation stimulus. DC secreted an average 3.5 nmol/l neopterin. In response to IFN-gamma, cells significantly increased their output of neopterin. In distinction to monocytes/macrophages, neopterin production in DC was highly sensitive to IFN-alpha and IFN-beta. Further, lipopolysaccharides (LPS) enhanced neopterin synthesis, whereas tumor necrosis factor alpha, interleukin (IL)-1beta, IL-2, IL-10, and IL-18 were ineffective. Simultaneously, tryptophan degradation by induction of indoleamine (2,3)-dioxygenase (IDO) was tested in stimulated cells. Our results showed that IFN-gamma as well as LPS are inducers of IDO in DC.

Cell Culture Techniques↗
PubMed2001

[Measurement of serum neopterin levels in patients with nasopharyngeal carcinoma and its significance].

OBJECTIVE: To evaluate the relationship between serum neopterin levels and nasopharyngeal carcinoma and its clinical significance. METHOD: The serum neopterin levels were determined in 54 patients with nasopharyngeal carcinoma (NPC group) and 32 healthy adults (normal group) by ELISA. RESULT: The serum neopterin levels in NPC group were significantly higher than that of in normal group (P < 0.001). The serum neopterin levels in UICC-TNM stages were undifferentiated (P > 0.05). The serum neopterin levels in patients with no lymph node metastasis were lower than that of in lymph node metastasis (P < 0.05). The serum neopterin levels decreased significantly after disappearance of tumor and its lymph node treated by radiotherapy (P < 0.01). CONCLUSION: Cellular immunity mediated by macrophages might be involved in the pathogenesis of nasopharyngeal carcinoma and the measurement of the serum neopterin may be a useful objective index to evaluate cellular immunological functions and curative effects.

Adult↗
PubMed2003

Urinary neopterin measurement as a non-invasive diagnostic method in pulmonary tuberculosis.

SETTING: Pulmonary department of a university hospital in Ankara, Turkey. OBJECTIVE: To investigate the usefulness of neopterin in pulmonary tuberculosis (PTB) as a rapid diagnostic tool. DESIGN: Neopterin concentrations in bronchoalveolar lavage fluid (BAL), serum and urine were measured in patients with PTB, with lung cancer and with pneumonia and in a healthy control group. RESULTS: In the BAL of PTB patients, serum and urine levels of neopterin were significantly higher than all the other groups (P < 0.001). Compared with the lung cancer group, PTB patients had higher neopterin in BAL and urine (P < 0.05). The PTB group had higher levels not only in BAL and urine, but also in serum, than the pneumonia group (P < 0.05). Compared with the pneumonia group and the healthy controls, neopterin levels in serum and urine were significantly higher in the lung cancer group (P < 0.05). In the PTB group, patients with moderately advanced PTB according to radiographic extent had higher levels of urine neopterin than patients with minimal disease (P = 0.01). CONCLUSION: Neopterin levels in BAL, serum and particularly in urine may reflect PTB activity before exact diagnosis of the disease by culture results, and correlates with radiological extent.

Adult↗
PubMed1992

Clinical significance of serum and urinary neopterin levels in patients with various liver diseases.

Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens.

Adolescent↗
PubMed1992

Highly sensitive, specific enzyme-linked immunosorbent assay of neopterin and biopterin in biological samples.

An enzyme immunosorbent assay of neopterin and biopterin on a polystyrene microtiter plate has been developed. A conjugate of neopterin or biopterin to bovine serum albumin was used to raise a specific antiserum against neopterin or biopterin in rabbits. An incubation mixture of the antiserum and samples prepared from human serum underwent another antigen-antibody reaction with the hapten fixed on the microtiter plate. The amount of antibody bound to the fixed hapten, which is inverse to the amount of hapten in the sample, was determined by using anti-rabbit IgG-horseradish peroxidase conjugate in a usual manner by measuring absorbance at 490 nm after reaction with o-phenylenediamine and hydrogen peroxide. The minimal detectable amounts of neopterin and biopterin were approximately 0.1 pmol. The specificity of the assay was so high that the assay system for neopterin completely distinguished it from biopterin, as judged from the cross-reaction of 0.002%, and vice versa. The amounts of neopterin and biopterin in human serum determined by the present method agreed well with those determined by high-performance liquid chromatography. We used the present method to determine the concentrations of neopterin in serum from healthy control subjects and patients with cancers and systemic lupus erythematosus; the results were consistent with literature data.

Biopterins↗
PubMed1992

Contrasting effects of interferon-gamma and interleukin-4 on neopterin generation from human adherent monocytes.

The production of neopterin is closely correlated with activation of cell-mediated immunity. Neopterin appears to be produced by human macrophages specifically stimulated with interferon-gamma (IFN-gamma). Interleukin-4 (IL-4), a B and T stimulatory factor, has recently been shown to inhibit monocyte/macrophage functions, including the ability to suppress monocyte-generated cytokines. In this report we confirmed previous studies that identified the monocyte/macrophage as the main producing cell among human blood cells and that secretion is stimulated by IFN-gamma and lipopolysaccharides (LPS). IL-4 inhibits the generation of neopterin from unstimulated monocytes. This inhibitory effect was dose dependent and occurred at concentrations lower than 0.01 ng/ml. However, IL-4 had only a minimal inhibitory effect on LPS-induced generation of neopterin and could not reverse IFN-gamma-induced neopterin secretion from adherent monocytes. Furthermore, we report that LPS induced IFN-gamma production in monocyte culture. This production is strongly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cells and provide further evidence that LPS-induced neopterin in macrophages may act by IFN-gamma-independent mechanisms.

Biopterins↗
PubMed2004

Time course of urinary neopterin in a non-Hodgkin's lymphoma patient during chemotherapy and radiotherapy.

The objective of this study was to follow urinary neopterin in a patient affected by non-Hodgkin's lymphoma during the three months treatment from the onset of the disease. In the study a patient affected by non-Hodgkin's lymphoma in Stage IV (centrocyto-centroblastic type) was enrolled. He was treated with combined chemotherapy and local radiotherapy. Neopterin was measured by high performance liquid chromatography in the first morning urine specimens. The time course of urinary neopterin levels ranged from 110 to 524 micromol x mol(-1) creatinine (mean 261, SD 67.5 micromol x mol(-1) creatinine). Over 70 % of the received values were higher than the upper limit of normal excretion of healthy subjects. Longitudinal analysis showed a relatively big variance of urinary neopterin with a tendency of decrease during the treatment. The significant decrease of urinary neopterin was observed till after the radiotherapy period which followed the chemotherapy period. In conclusions, the response to the therapy was accompanied by a reversal tendency of neopterin excretion to physiological values. This study confirms neopterin as a suitable additional parameter for the control of non-Hodgkin's lymphoma therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Serum neopterin levels in HIV infected patients with & without tuberculosis.

BACKGROUND & OBJECTIVE: Three categories of prognostic markers are best documented as having significance in relation to prognosis of HIV infection. These include HIV viral load, CD4 T-cell levels and plasma levels of soluble markers of immune activation. The plasma activation markers, like neopterin, tumor necrosis factor alpha (TNF-alpha), interleukins etc., are products of cytokine activity and represent immunologic changes throughout the body. There is not much information available on serum neopterin estimation in patients infected with both HIV and tuberculosis (TB), though neopterin levels are known to be elevated in pulmonary TB patients. In this study we attempted to correlate neopterin levels with the presence of tuberculosis in HIV infected and uninfected individuals and studied the changes after antituberculosis treatment. METHODS: Serum neopterin concentrations were measured by high performance liquid chromatography (HPLC) in 25 HIV-seropositive (HIV-TB) and 10-seronegative (TB) patients with tuberculosis before, during and at the end of antituberculosis therapy (ATT). S-neo was also measured in 10 HIV-seropositive asymptomatic individuals and 10 healthy controls. The results were correlated with clinical, bacteriological and immunological status. RESULTS: All TB patients regardless of HIV status had elevated s-neo concentrations at diagnosis, which declined gradually during treatment. Patients with HIV/TB with CD4 counts < 200/mm(3) had the highest levels at baseline with a steep fall during treatment. The median level at the end of treatment was significantly higher in HIV/TB than in TB patients, despite clinical improvement and bacteriological clearance of Mycobacterium tuberculosis. HIV infected asymptomatic individuals had neopterin levels that were higher than healthy controls but lower than HIV-TB patients. INTERPRETATION & CONCLUSION: Serum neopterin levels are elevated in HIV-positive patients, with the highest levels in those with tuberculosis and CD4 counts < 200/mm(3). Though the levels decrease with anti tuberculosis therapy, persistently elevated levels indicate progressive HIV disease and a poor prognosis.

Adult↗
PubMedDate not supplied

Neopterin, a marker of cell-mediated immune activation in human pregnancy.

High neopterin excretion is closely associated with activation of cell-mediated immunity. We studied urine and serum neopterin concentrations and serum interferon-gamma concentrations in normal pregnant women. In our study population, neopterin concentrations exceeded the normal range in 663 of 840 samples (79%). Neopterin levels increased with the time of pregnancy. Serum samples drawn from women in the third trimester of pregnancy also showed high neopterin concentrations in almost all cases; however, no circulating interferon-gamma was detected. Whereas neopterin is able to penetrate into the blood stream because of its small size (M = 253 D), diffusion of interferon-gamma is limited. Raised neopterin levels provide evidence for activated cell-mediated immunity during pregnancy.

Adult↗
PubMed1991

Relationship between urinary neopterin excretion and islet cell antibodies in type 1 (insulin-dependent) diabetes.

Neopterin is specifically produced by interferon-activated macrophages, and it may be considered a marker of cellular immunity. In 40 newly diagnosed and 38 longer standing type 1 (insulin-dependent) diabetics the relationship between urinary neopterin levels and islet cell antibodies (ICA) was investigated. Raised urinary neopterin levels were found in 30 ICA positive (mean +/- SD: 729.8 +/- 602.1 mumol/mol creatinine, p = 0.0001) and 10 ICA negative (433.4 +/- 191.2 mumol/mol creatinine, p = 0.0005) diabetics at onset of disease compared with age-matched control subjects (118.1 +/- 33.2 mumol/mol creatinine). No significant difference in urinary neopterin levels was observed between diabetic groups. After the first stages of disease (greater than 5 months from onset), a significant difference (p = 0.0002) in urinary neopterin excretion was found between longer standing ICA positive patients and controls, but not between ICA negative diabetics and controls. In longer standing diabetics, neopterin levels were significantly higher in ICA positive patients than in ICA negative patients (544.6 +/- 341.3 versus 201.7 +/- 180 mumol/mol creatinine, p = 0.0002). No correlation between newly diagnosed or longer standing patients and HbA1c levels was found. Our results suggest that increased neopterin excretion in type 1 diabetes seems to be a sensitive indicator for the activation of cell-mediated immunity even when ICA are undetectable.

Adolescent↗
PubMedDate not supplied

[The level of neopterin in the plasma of patients with acute kidney failure during treatment with continuous arteriovenous hemofiltration].

Neopterin is a biochemical marker of cellular mediated immune reactions and may be used in elucidating the cause of acute renal failure. 9 patients (6 males, 3 females) aged 23 to 56 years suffering from a severe form of the disease were examined. A continuous arteriovenous hemofiltration was used as a treatment with exchanging 29.2 +/- 2.0 (14-65) kg of fluid during 24 hours. The patients' diet included protein and amino acids of 1.2-1.5 g/kg of body weight, 35-45 Kcal/kg of body weight per 24 hours with meal and parenteral infusions. 4 patients died. Contents of neopterin in the plasma of the healthy equaled to 6.8 +/- 03 (3.4-11.3) nmol/l (radioimmunoassay; Henning; Berlin, GmbH). In patients with acute renal failure plasma neopterin contents were increased, i.e. 130.0 +/- +/- 9.6 (48.2-200.2) nmol/l and in two thirds of the cases and correlated with creatinine levels (r = + 0.60 +/- 0.17; p less than 0.05; n = 23), thus showing a simultaneous influence of anuria and continuous arteriovenous hemofiltration on a neopterin pool amount at the same time, in patients with tropical malaria and hemotransfusion shocks (2 cases), the neopterin contents were extremely high and did not correlate with the creatinine level. During continuous hemofiltration at a rate of 21.6 +/- 1.3 (15.9-36.9) ml/min neopterine clearance was 17.2 +/- 2.1 (6.7-36.2) ml/min. Neopterin hyperproduction after blood transfusion suggests an immune conflict as a possible cause of acute renal failure.

Acute Kidney Injury↗
PubMed1991

Postmortem evaluation of serum and urine neopterin concentrations.

Cellular immune response is accompanied by the release of neopterin. Increased neopterin levels in urine and serum are observed in patients during viral infections, autoimmune diseases, and allograft rejections and certain malignant diseases. We investigated postmortem neopterin concentrations in urine and serum samples taken from 32 corpses 3 to 69 h (mean 19.3 h) after death. Urine neopterin concentrations in corpses are similar to those of healthy live controls and are independent of the time after death. In contrast, serum neopterin concentrations are frequently greatly increased in corpses, and the levels are higher in sera collected more than 10 h after death in comparison with samples obtained earlier. Neopterin measurement in urine and serum samples of corpses is feasible. It appears likely that urine neopterin concentrations could aid the diagnosis of inflammatory diseases in corpses.

Adult↗