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PubMed1991

Predictive value of interleukin-6 and neopterin in patients with multiple myeloma.

Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman's rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models.

Aged↗
PubMed1989

Neopterin excretion after liver transplantation and its value in differential diagnosis of complications.

The aim of this study was to investigate patterns and clinical utility of a neopterin marker in liver allograft recipients. Urinary neopterin levels were studied in 59 transplant patients daily until discharge. During the early postoperative period (days +1 to +20) neopterin excretion exhibited a liver-specific pattern that clearly differed from that seen in renal and bone marrow transplant recipients. Neopterin concentrations increased and reached peak values on day +7. The height of this early peak varied in context with complications such as infection or rejection, and was correlated with an unfavorable prognosis. In contrast to the early phase, no liver-specific pattern was observed after day 20. As seen in all other transplant patient populations, values normalized in patients with an uncomplicated course but again increased during infection or rejection episodes. Neopterin levels were particularly high during CMV infection, and their increments were directly related to the severity of CMV disease. The neopterin marker, although not specific, enables discrimination between patients with a complicated and uncomplicated clinical course. High neopterin values early after transplantation are associated with unfavorable prognosis and correlate with an increased risk of developing CMV disease.

Biopterins↗
PubMed1987

[Initial experiences with the determination of neopterin in the urine of females with genital and breast tumors].

The quantitative analysis of urinary neopterin was carried out ahead of the operation by means of high performance liquid chromatography (HPLC). The sample included 98 women with genital or breast neoplasias. Significant differences have been found between the patients with benign or preinvasive neoplasias as well as women with malignancies (p less than 0.001) as compared to a control group of healthy females. The neopterin levels of the malignant tumors were definitely higher than those of the benign tumors (p less than 0.01). As far as genital tract cancer ist concerned, the neopterin levels found were in 51.5 per cent of the cases above the estimated limit with a specificity of 95.1 per cent in healthy patients and 79.5 per cent within the group of nonmalignant gynecologic lesions. The neopterin levels established in patients with genital tract malignancies appear to be related with the stage of the development of the disease (i.e. levels and positive rate are significantly higher in stages III and IV as compared to stages I and II; p less than 0.01). Tests of women with breast cancer showed the smallest number of raised neopterin levels. The average level of the last mentioned cases didn't differ greatly from the levels of the benign breast tumors. Tests of the patients with cancer after treatment showed in 68.8 per cent of all cases neopterin levels corresponding to the clinical findings. However, cases of smaller recurrent tumors may be accompanied by normal neopterin levels as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopterins↗
PubMed1993

Neopterin in the diagnosis of disorders associated with immune system activation.

While the knowledge concerning the role of the immune system in many internal disorders has grown rapidly in recent years, there are few methods to assess immune system activation in clinical practice. Measurement of urine neopterin, product of a metabolic pathway controlled by interferon-gamma, has been found useful in many clinical conditions. The present study concerns neopterin excretion in 157 patients with different internal disorders. As expected, we found an increase in urine neopterin in patients with malignant tumors, autoimmune disorders like systemic lupus erythematosus or inflammatory bowel disease, and infections. Elevated neopterin levels were also observed in acute pancreatitis and in acute myocardial infarction. In addition, significant correlations between urine neopterin and zinc and neopterin and copper excretion were found suggesting a physiological role of neopterin as urine antioxidant.

Adult↗
PubMed1993

Neopterin and prognosis in patients with adenocarcinoma of the colon.

Concentrations of neopterin, a sensitive indicator for the activation of cellular immunity, were measured in urine samples of 44 patients with adenocarcinoma of the colon at diagnosis. To judge the relative predictive value of neopterin concentrations, other routine clinical and laboratory variables were concomitantly determined. The patients were then followed up to 10 yr, and the abilities of all variables to predict death from cancer were assessed. Neopterin concentrations were not correlated with either tumor stage or Dukes' stage. In univariate analyses using the product-limit approach, four variables were significant indicators of poor prognosis: presence of distant metastases (P = 0.0001); high Dukes' stage (P = 0.0009); high urinary neopterin concentration (P = 0.0034); and advanced stage (P = 0.030). Presence versus absence of lymph node metastases was not associated with prognosis. Multivariate survival analyses by the proportional hazards technique demonstrated that neopterin provided statistically independent predictive information in addition to either presence versus absence of distant metastases or Dukes' stage. When neopterin and tumor stage were investigated for joint prediction, stage failed to be included in the model. Thus, neopterin concentrations provide valuable and statistically independent prognostic information in patients with adenocarcinoma of the colon.

Adenocarcinoma↗
PubMed1996

[Cerebrospinal fluid neopterin levels in children with neurologic diseases].

Neopterin has been determined in blood as a marker of cellular immune system activation. We studied cerebrospinal fluid (CSF) neopterin levels in children with neurologic diseases, and the following results were obtained: (1) CSF neopterin levels markedly increased at the acute phase of bacterial meningitis, aseptic meningitis, and encephalitis as compared with those in patients without neurologic diseased. (2) In the CSF of patients with bacterial meningitis and aseptic meningitis, neopterin levels decreased more rapidly than the total cell count and 2'5' oligoadenylate synthetase (2-5 AS) did. (3) CSF neopterin in patients with non-infectious neurologic diseases was almost equal to that in patients without neurologic diseases. (4) There was no correlation between CSF neopterin and other CSF values, such as total cell count, mononuclear cell count, protein, and 2-5 AS. These results suggest that CSF neopterin is a useful marker of inflammatory central nervous diseases.

Adolescent↗
PubMed1996

[Urinary excretion of neopterin and plasma levels of interferon gamma in patients with multiple myeloma].

Neopterin, a pteridine derivate, is produced and released by lymphocytes and monocytes/macrophages after stimulation by T-cell derived interferon (IFN) gamma. The urinary excretion of neopterin and plasma IFN-gamma levels were measured in 35 patients with multiple myeloma (MM) and 21 patients with other monoclonal gammapathies (MG). Significantly higher excretion of neopterin was found in patients with MM in the time of diagnosis and/or progressive phase of disease (median 963,7 mumol/mol creatinine, range 183,9-2 376,3) comparing the patients in stable phase of MM (median 407,4, range 184,3-826,4), monoclonal gammapathy of undetermined significance (406,2, 226,9-1 689,3) and other MG (452,5, 240, 4-913,6) (p < 0,05). Elevation of urinary neopterin levels preceded changes of other parameters of disease activity by several months, persistent high urinary excretion was associated with refractory disease respectively. The differences of neopterin levels between patients of various clinical stages of MM was observed in newly diagnosed and progressive disease (III. vs. I and II. clinical stage, p < 0.05), but not in stable phase of MM. The plasma concentration of IFN-gama were insignificantly higher in MM than in health controls, however, the difference between all groups of patients was not found. We conclude, that neopterin is a good marker of disease activity in patients with MM. The plasma levels of its regulatory cytokine, IFN-gama, did not correlate with urine neopterin levels in our study.

Adult↗
PubMed1998

[Neopterin: laboratory marker of cellular immunity activation in rheumatoid arthritis].

AIM: Measurement of neopterin in the serum of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 59 patients with verified RA diagnosis (22 cases of joint lesion stage I-IIa, 27 of stage IIb-IIIa, 10 of stage IIIb-IV established roentgenologically, 48 patients were seropositive by IgM-rheumatoid factor) were examined for concentrations of serum neopterin and C-reactive protein (CRP). The activity and prognostic factors were characterized by modified Wilke method, the severity index was calculated. 100 healthy donors served controls. RESULTS: Immune inflammation in RA develops with growing neopterin concentration in the serum. This concentration well correlates with inflammation activity and intensification of systemic symptoms. CONCLUSION: Neopterin measurements may be important for determination of inflammation activity in RA. Further efforts should be made to ascertain relationships between neopterin hyperproduction and disturbances of cellular immunity in RA, clinical value of neopterin assays compared to the other laboratory evidence, feasibility of using neopterin levels to define prognosis and efficacy of on-going therapy.

Adolescent↗
PubMed1985

Significance of urinary neopterin in patients with malignant tumors of the genitourinary tract.

The urinary neopterin excretion was measured by high-performance liquid chromatography in 417 healthy subjects and in 76 patients with clinically and pathohistologically verified neoplasias of the urinary tract (bladder tumor, carcinoma of the prostate, and renal cell carcinoma). The patients with early tumor stages both with bladder tumor and carcinoma of the prostate had normal urinary neopterin levels, except one patient with bladder tumor who had a value at the upper confidence limit. Of 40 patients with higher stages of bladder tumor and carcinoma of the prostate, 35 had elevated urinary neopterin levels. Two of 10 patients with bladder tumor in stage T3, 1 of 4 patients with carcinoma of the prostate Stage C, and 2 of 15 patients with prostatic cancer Stage D showed normal neopterin levels. The patients with renal cell carcinoma did not demonstrate any definite correlation between tumor stage and urinary neopterin excretion. The current study suggests that the neopterin assay may supplement laboratory measurements in tumors of the urinary tract, providing helpful information regarding case selection for the most convenient therapeutic management and postoperative follow-up.

Adolescent↗
PubMed1990

Urinary neopterin excretion in patients with uterine sarcomas.

Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. Urinary neopterin concentrations were measured in a total of 44 patients with uterine sarcomas. Pretherapeutic neopterin excretions were elevated in 78% (14/18). The mean neopterin concentration of patients with sarcomas was significantly higher (P less than 0.0001) than that obtained in women with benign myomas and healthy controls. Furthermore, a significant correlation of normal or raised neopterin concentrations with the clinical course of disease was found. These data suggest that urinary neopterin measurement might be a useful immunologic marker for women with uterine sarcomas.

Adolescent↗
PubMed1991

Neopterin and beta 2-microglobulin and the assessment of intra-blood-brain-barrier synthesis of HIV-specific and total IgG.

In HIV-seropositive patients, we evaluated the clinical utility of measuring combinations of serum and CSF levels of neopterin and beta 2-microglobulin (beta 2-M) (by RIA), as well as the intra-blood-brain-barrier (IBBB) IgG synthesis rate, IgG index, and HIV antibody index (by rate nephelometry, EIA, and formulae) for the assessment of HIV infection of the CNS. We studied paired sera and CSF from 31 HIV-seropositive patients: asymptomatic (16), ARC (12), and AIDS (3). A normal serum neopterin level predicts normal levels of serum beta 2-M, CSF neopterin, or CSF beta 2-M in 90%, 100%, and 100%, respectively, of our patients. An elevated serum neopterin level predicts an elevated level of serum beta 2-M or CSF neopterin in 81% and 62%, respectively, of cases. The HIV antibody index and IBBB IgG synthesis rate or IgG index must be determined separately because they do not predict each other and are not predicted by levels of neopterin or beta 2-M.

Antibodies, Viral↗
PubMed2005

Serum levels of neopterin and interleukin-2 receptor in women with severe preeclampsia.

Preeclampsia continues to be a major cause of maternal and perinatal mortality and morbidity worldwide. The etiopathogenesis of preeclampsia is not fully understood. Neopterin and interleukin-2 (IL-2) production reflects cellular immunity. Our purpose was to determine the levels of neopterin and interleukin-2 receptor (IL-2R) in pregnant women with severe preeclampsia, and assess the implications of these findings in the pathophysiology of preeclampsia. Fourteen women with preeclampsia were compared with 14 healthy pregnant women. Serum levels of neopterin were measured by an enzyme-linked immunoassay (ELISA), and IL-2R levels were determined by an immunoassay method with an Immulite analyzer. The levels of neopterin and IL-2R were significantly higher in the preeclamptic subjects than in normotensive women (P<0.05). There was a significant correlation between neopterin and IL-2R. We found that serum neopterin and IL-2R levels are increased in women with severe preeclampsia. The results of this study suggest that a T-helper 1 (Th1) type immune mechanism is involved in the pathogenesis of preeclampsia.

Adult↗
PubMed1994

Neopterin production by HIV-1-infected mononuclear phagocytes.

Neopterin is a pteridine produced by human mononuclear phagocytes, usually in response to interferon-gamma (IFN-gamma) stimulation. Increasing serum levels of neopterin correlate with clinical progression to AIDS in HIV-infected people, but the factors that contribute to these elevated levels are not established. We performed in vitro experiments to investigate the possibility that HIV-1 infection of mononuclear phagocytes directly induces enhanced neopterin production. We found that HIV-1-infected monocytes and peritoneal macrophages produced neopterin in quantities similar to amounts produced by uninfected cells. The HIV-infected cells responded to stimulation with IFN-gamma as well as uninfected cells, with a 6- to 12-fold increase in neopterin production. We conclude that elevated serum levels of neopterin in HIV-infected individuals are not caused by HIV-1 infection of mononuclear phagocytes but may be a result of the normal response to mononuclear phagocytes to increased levels of IFN-gamma.

Biopterins↗
PubMed1998

Neopterin derivatives modulate the nitration of tyrosine by peroxynitrite.

The impact of neopterin and 7,8-dihydroneopterin on peroxynitrite-induced nitration of l-tyrosine was studied. Neopterin derivatives and peroxynitrite are formed during immune response. Tyrosine nitration represents one major effect of nitric oxide-mediated cytotoxicity. Peroxynitrite formed in situ was co-incubated with tyrosine and neopterin or 7,8-dihydroneopterin or other pteridine derivatives, respectively. The nitration product, 3-nitro-l-tyrosine, was measured by HPLC via UV absorption at 360 nm. Neopterin (200 microM) increased the nitration rate between pH 4.0 and 5.5 up to +60%. 7,8-Dihydroneopterin inhibited tyrosine nitration over the whole pH range examined. In a series of various pteridine derivatives, neopterin and 7,8-dihydroneopterin achieved the strongest modulating effects on tyrosine nitration. Interactions of peroxynitrite with hydroxypropyl side chains of fully aromatic pterin derivatives may increase nitration, while partially hydrated pyrazino ring structures abate the reactivity of peroxynitrite. The results of this study suggest a potential impact of neopterin derivatives on peroxynitrite-mediated cytotoxicity.

Hydrogen-Ion Concentration↗
PubMed1995

Serum-soluble receptors for tumor necrosis factor-alpha and interleukin-2, and neopterin in acute rheumatic fever.

Immune activation may play an important role in the pathogenesis of acute rheumatic fever (ARF). The objective of the present study was to investigate serum concentrations of various markers of immune activation in ARF patients. Sera of 32 patients with ARF were investigated, 20 of them in follow-up. Radioimmunoassay was used to quantify neopterin and ELISA for the measurement of 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R) and soluble interleukin-2 receptor (sIL2-R). Markers of immune activation were found to be raised in 48% (sTNF-R), 28% (sIL2-R), and 78% (neopterin) of patients at the onset of ARF. There were significant correlations between the concentrations of neopterin and sTNF-R (rs = 0.60, P < 0.001) or sIL2-R (rs = 0.35, P < 0.05). Higher neopterin concentrations were found in patients with combined aortic and mitral insufficiency than in patients with mitral valve lesions alone (U = 2.67, P < 0.05) or without valve lesion (U = 2.36, P < 0.05). Increased concentrations of neopterin, sTNF-R, and sIL2-R demonstrate activation of the cellular immune system in patients with ARF. Higher serum neopterin concentrations are associated with development of combined aortic and mitral insufficiency during the first episode of ARF.

Acute Disease↗
PubMed2003

Kynurenine and neopterin in the aqueous humor of the anterior chamber of the eye and in serum of cataract patients.

Serum kynurenine, neopterin, selenium concentrations; neopterin concentrations in aqueous humour from anterior chamber of eye and selenium content in lenses were determined in 40 catarat patients with and in 51--without pseudoexfoliation (PES). Significantly increased kynurenine and neopterin levels in serum and neopterin concentration in aqueous humour were observed in mature cataract patients with PES compared to whose without. These patients also presented with the lowest content of selenium in serum and lens, compared with cataract patients without PES. Increased concentrations of neopterin in serum and aqueous humour of anterior chamber of eyes suggest an increased degree of oxidative stress in patients with PES. Thus, the results support the role of oxidative stress in the development of PES in cataract patients. The decreased content of selenium may elicit immune system activation via an increased oxidative stress as it is indicated by the increased formation of kynurenine and neopterin.

Aged↗
PubMed1999

The influence of kynurenine, neopterin, and norepinephrine on tubular epithelial cells and alveolar fibroblasts.

We have examined the effect of kynurenine, neopterin and norepinephrine on epithelial cells and fibroblasts: the total DNA synthesis (by adding 3H-thymidine), the mitotic index, the amount of pathological mitosis and apoptosis. We have observed that kynurenine, neopterin and norepinephrine induce pathological mitosis and apoptosis of epithelial cells of kidney. The total DNA synthesis increases by the incubation of the epithelial cells with neopterin and norepinephrine. We have found an increase of pathological mitosis after addition of kynurenine, neopterin and norepinephrine to fibroblast cell culture. The total DNA synthesis is promoted by neopterin and norepinephrine, while kynurenine does not alter it. These data allow us to suggest that kynurenine, neopterin and norepinephrine promote epithelial cell damage leading to cell death through apoptosis, and can therefore be added to the factors, which promote the pathological mitosis of fibroblasts.

Animals↗
PubMed1987

[Neopterin in the serum and urine in the differential diagnosis of disorders of kidney function following kidney transplantation].

In a period of 10 months neopterin in serum and urine was determined by radioimmunoassay in 33 renal allograft recipients treated with cyclosporin A. While in allograft rejections the highest neopterin concentrations were found in the serum, patients with viral infections after renal transplantation showed the most elevated concentrations in the urine. For early diagnosis of allograft rejection the ratio of neopterin clearance and serum-neopterin was the most significant criterion of the parameters measured in this study. Patients without complications during the follow-up showed slightly elevated and stable neopterin levels in serum and urine. The presented results indicate that neopterin is a useful parameter for the follow-up after renal allograft transplantation and for the diagnosis of immunological complications.

Adult↗