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PubMed2006

Serum interleukin-2 and neopterin levels as useful markers for treatment of active pulmonary tuberculosis.

Macrophages and T cells are responsible for the main immune response to tuberculosis by secreting many cytokines and other substances. The aim of this study was to determine the effects of multidrug treatment on serum levels of interleukin-2 (IL-2), secreted by activated T cells, and of neopterin, secreted by macrophages and monocytes, in patients with pulmonary tuberculosis. The study included 30 patients with active pulmonary tuberculosis, confirmed by the detection of acid-fast bacilli in direct sputum smears and/or sputum cultures. The serum levels of IL-2 and neopterin were measured before and during the treatment and compared with 15 patients with inactive pulmonary tuberculosis and 15 healthy controls. Serum IL-2 and neopterin levels were higher in patients with active tuberculosis (164.53 +/- 58.91 pg/ml and 69.54 +/- 29.42 nmol/l, respectively) than those in inactive tuberculosis (95.43 +/- 31.17 pg/ml and 10.71 +/- 1.78 nmol/l) or controls (79.20 +/- 14.81 pg/ml and 9.50 +/- 2.27 nmol/l) (p < 0.001 for each parameter). No significant differences were found in IL-2 and neopterin levels between inactive tuberculosis and control subjects. The IL-2 levels remained elevated in active tuberculosis at 2nd month of treatment (p < 0.001) and decreased to the control levels after 4th month. Neopterin levels were significantly higher in active tuberculosis than those in inactive tuberculosis or controls at the 2nd and 4th months of treatment. These findings indicate that measurements of serum IL-2 and neopterin levels are useful in following up the treatment and immune response to tuberculosis.

Adolescent↗
PubMed2002

Immune monitoring in organ transplantation using neopterin.

Transplantation has become an established and successful therapy. Rejections and infections are the principal immune-related complications in the post-transplant course. A reliable and early diagnosis is necessary to prevent graft failure and patient morbidity. Despite the immunologic nature of these complications the diagnostic procedures still rely on functional tests and organ biopsies. Non-invasive monitoring remains to be one of the major goals in transplant medicine. Neopterin is a sensitive marker of the cellular immune response. It reflects the activation of macrophages and can be easily measured in serum, plasma, urine or other body fluids. This review summarises studies on the diagnostic value of neopterin in transplant medicine. Based on these results key factors for immune monitoring in regard to neopterin are evaluated. In particular the unspecificity of diagnostic immune markers, the kinetics of the immune response, the importance of adjustment of neopterin to kidney function, and quantitative differences in immune pathways against viruses and allografts are discussed. Reflecting these points a concept to use neopterin for non-invasive immune monitoring in the clinical routine is presented. This approach calculates probabilities for specific post-transplant complications based on daily measurements of neopterin, a combination with the acute phase reactant amyloid A, and a modification of the likelihood ratio concept.

Animals↗
PubMed1999

Dihydropteridine reductase activity and neopterin levels in leukemias and lymphomas: is there any correlation between these two parameters?

Urinary neopterin levels, blood dihydropteridine reductase activity as well as other frequently used clinical parameters were evaluated in 110 patients suffering from various types of lymphomas and leukemias. Among them neopterin was detected as the most sensitive marker representing the severity of malignancy (p<0.00001). All patients with active diseases had significantly raised urinary neopterin levels compared to those in remission and healthy controls. Of 69 patients with active disease 66 (96%) were above the upper limit seen in healthy subjects. In addition, the highest neopterin excretion was found in patients with active chronic myeloid leukemia (1469+/-479 micromol/mol creatinine n=16). In contrast, only 1 of 41 patients in stable responsive disease and remission (2.4%) had increased urinary neopterin levels above the upper limit. Dihydropteridine reductase (DHPR) activities were also detected in all patients and control groups. In active disease slightly reduced (DHPR) activities were evident (3.42+/-0.37 for controls, 2.92+/-0.39 in active disease and 3.28+/-0.42 nmol red cytochrome C/min/5 mm diameter disc in remission patients). However in patients under medication this was strengthened. This data also suggest that DHPR activity can be effected by chemotherapy. The results of the present study support the fact that urinary neopterin levels may be an useful and reliable early prognostic marker for neoplasia when used together with other prognostic indicators. Our data also suggest that reductions in DHPR activities may also be an underlying cause for the neurological disorders that are commonly seen in patients with haematological malignancies.

Biomarkers, Tumor↗
PubMed2002

[Serum neopterin and beta2-microglobulin concentration as "prognostic markers" of AIDS].

UNLABELLED: The aim of the study was evaluation of serum neopterin and beta 2-microglobulin concentrations as "prognostic markers" of AIDS natural history. MATERIAL AND METHODS: Investigations was performed in 68 patients (48 hiv-infected and 20 without hiv-infection), who were divided into 3 groups according to HIV CDC classification. RESULTS: The highest serum concentrations of neopterin and beta 2-microglobulin were detected in patients with AIDS. In a non-symptomatic HIV-infected patients p24 Ag was absent. It was detected in patients with AIDS. Negative correlation between neopterin and beta 2-microglobulin serum concentration and CD4 count was detected in sera from all patients. Positive correlation was observed between p24 Ag, serum neopterin and beta 2-microglobulin concentration in patients with AIDS. CONCLUSIONS: Progression of HIV infection was connected with an increase of serum neopterin and beta 2-microglobulin serum concentrations. Neopterin serum concentration seems to be a more sensitive marker of HIV infection than beta 2-microglobulin.

Acquired Immunodeficiency Syndrome↗
PubMed2001

[Effect of langchuangding on serum soluble interleukin-2 receptor and neopterin level in patients of systemic lupus erythematosus].

OBJECTIVE: In order to explore the therapeutic mechanism of Langchuangding (LCD) in treating systemic lupus erythematosus (SLE) by observation of its effect on serum soluble interleukin-2 receptor (sIL-2R) and neopterin level in SLE patients. METHODS: Forty-five patients of SLE were randomly divided into two groups, the 25 cases in the treated group were treated with LCD plus glucocorticoid (GCC) and the 20 cases in the control group were treated with GCC alone. The levels of sIL-2R and neopterin were observed before and after treatment by double antibody sandwich ELISA. RESULTS: SLE patient showed higher levels of sIL-2R and neopterin than normal, and being higher in active stage than in remission stage. The level of neopterin was positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.86, P < 0.01). After treatment, the levels of sIL-2R and neopterin were lowered significantly in the treated group than those in the control group (P < 0.05). CONCLUSION: LCD could effectively reduce the serum levels of sIL-2R and neopterin in SLE patients, which would be beneficial to cellular immune functional regulation and induce the disturbed internal environment of immunity to homeostasis.

Adolescent↗
PubMed1992

The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals.

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo-controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and beta 2-microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum beta 2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and beta 2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or beta 2M tended to maintain lower levels of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1992

[The serum neopterin level in acute rheumatic fever].

Acute rheumatic fever (ARF) is a systemic inflammatory disease etiologically related to infection with group A streptococcus characterized by a broad spectrum of disorders of cellular and humoral immunity. To estimate the activity of the immunopathological process and to forecast myocardial derangement in ARF patients, measurements were made of neopterin in the serum of ARF patients. Nine men with ARF serving in the armed forces were examined. The control group comprised 24 donors. The reference group included 13 patients with dilated cardiomyopathy and 14 with chronic myocarditis. The mean level of neopterin in ARF patients was equal to 14.5 +/- 12.2 nM/l and was significantly higher than in the donors (5.0 +/- 2.0 nM/l). In patients with dilated cardiomyopathy and chronic myocarditis, it was 9 +/- 6 and 16 +/- 11 nM/l, respectively. On more careful clinical analysis the highest level of neopterin was recorded in 3 patients with impairment of the valvular apparatus of the heart. That level was observable during the whole period of the follow-up of the patients. In other patients, no impairment of the valves was detected, whereas the concentration of neopterin fell to normal. Therefore, the rise of the level of neopterin was described for the first time in patients with ARF. Besides, a relationship was found between the high level of neopterin and impairment of the valvular apparatus of the heart.

Adolescent↗
PubMed2004

[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes].

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.

Adult↗
PubMed2004

The detection of urinal neopterin concentration increases the efficiency of cervical smear in the diagnosis of cervical cancer.

OBJECTIVE: To investigate the importance of urinal neopterin detection carried out together with cervical smear test, in the diagnosis of cervical cancer. METHODS: In this study, urine samples were collected from randomly selected vulvovaginitis' women who attended hospital and an independent control group. The participants were classified into two representative sample groups and a control group; 1st Group: 35 women with vulvovaginitis, whose ages varied from 21 to 42 and who had no viral infections, and chronic inflammatory diseases and no smoking habit, but had complaints of vaginal discharge. 2nd Group: 25 women aged between 38-52 with no smoking habit, who applied to hospital with complaints of vaginal discharge, and cervical cancer was diagnosed for them as the result of biopsy, but no associated treatment of cancer had been carried out yet. 3rd Group: A control group with 30 women who aged between 20 and 28, with no smoking habit, and who had not taken part in sexual activities yet. They had no complaints from any type of tumors, and viral infections or chronic inflammatory diseases. Urinalysis was carried out for each group member's urine sample in order to measure the level of neopterin. Neopterin was estimated by HPLC. Some statistical analyses were done by SPSS Windows 10.0 and were analyzed by Oneway Annova test. (p=0.000) Meaningful differences between the groups were determined by Post Hoc Tukey Test. RESULTS: The mathematical results of neopterin levels for the groups revealed that the level of Group 1 was significantly higher than the level of Group 3 (p= 0.0001). When the levels of Group 1 and 2 were compared with each other, a significant difference was determined (p=0.004). Also, the difference in the levels of Group 2 and 3 was found to be significant (p=0.0001). CONCLUSIONS: If the results of this study were not confounded by another factor, then we can deduce that an increment in the level of neopterin may be considered as a risk factor that should warrant further investigation of cervical cancer. Then, the detection of urinal neopterin level as a noninvasive test done together with cervical smear can increase the sensitivity of smear test.

Adult↗
PubMed2005

Serum neopterin levels in patients with chronic hepatitis B.

The aim of this study was to determine the neopterin levels and peripheral blood lymphocyte subgroups in HBeAg-positive and -negative chronic hepatitis B patients. A total of 89 patients were included in the study. The mean serum neopterin level of patients with chronic hepatitis B was significantly higher than that of the control group. In HBeAg-positive chronic hepatitis B patients, the mean serum neopterin level was significantly higher than that of anti-HBeAb-positive patients. There was no significant correlation between the serum neopterin levels and alanine aminotransferase and HBV-DNA levels in HBeAg-positive chronic hepatitis B patients. There were no significant differences between the control subjects and patients with HBeAg-positive or anti-HBeAb-positive hepatitis in terms of the percentage of peripheral blood CD4+ or CD8+ or the ratio of CD4+/CD8+ lymphocytes. Our results suggest an association between elevated neopterin concentrations and HBeAg-positivity in patients with chronic hepatitis B. However, there appears to be no association between the neopterin levels and either hepatocyte damage or viral replication status.

Adolescent↗
PubMed2004

Serum levels of neopterin in patients with lichen planus.

Lichen planus (LP) is a chronic dermatosis whose clinical features include mildly erythematous to violaceous flat-topped, polygonal papules. The etiology of lichen planus is unknown, but it has been postulated that immune mechanism is important. Although it is of importance to monitor the course of immune-mediated diseases, there is a limited number of reliable biomarkers which can be used for lichen planus. Neopterin (NP), a 2-amino-4-hydroxy-(1'2'3'-trihydroxypropyl)-pteridine, is secreted by monocytes and macrophages, mainly as a response to INF-gamma secretion by activated T-lymphocytes. Therefore NP may be a sensitive marker of T-cell mediated immunity. The aim of the presented study was to assess the serum levels of neopterin in patients with lichen planus and to investigate whether serum neopterin levels reflect extensive lesions and progression of this disease. We studied 66 patients with lichen planus who were classified into one of two diagnostic groups: Group I comprised 33 patients with generalized lesions; group II comprised 33 patients with circumscribed lesions. The control group consisted of 30 healthy sex- and age-matched individuals. The serum neopterin concentrations were measured with a commercially available enzyme-linked immunosorbent assay kit. The results of our study are summarized in Table 1. In our study, the serum neopterin levels in the patients with lichen planus classified to group I (9.12 +/- 4.39 ng/mL) and group II (3.80 +/- 0.68 ng/mL) as well as in the whole collection of patients (group I and group II; 6.55 +/- 2.30 ng/mL) were significantly higher than those of the control subjects (2.55 +/- 0.34 ng/mL). Our findings confirm a role for enhanced cellular immunity as well as macrophages activation observed in lichen planus. It seems to us that evaluation of serum neopterin levels, despite the relatively low specificity, reflects extensive lesions and lichen planus progression.

Adolescent↗
PubMed2006

[Neopterine and ige during respiratory-syncytial virus infection in infants].

The number of studies confirms the correlation between IgE and neopterine levels. One of the forms of revelation of the immune answer of T-cells is the activation of T-cell system, that in its turn results in secretion of IL-2 and INF-gamma by Th-1 subtype cells. Activation of macrophages by INF-gamma the human organism. The target of our research was the evaluation of the role of the marker of macrophage activation -- neopterine in children with recurrent wheezing developed during onset of RSV infection and possible connection with IgE level. In the study 52 children of age from 1 to 12 months having RS-virus infection were included. Two groups were determined as controls -- group of healthy children and children with wheezing of non RSV etiology. Determination of neopterine was performed by enzyme immunoassay method (ELISA). During the RS-virus induced acute respiratory infection the rate of neopterine in the blood serum was significantly decreased in the group of patients with recurrent wheezing in comparison with the I group (first episode of wheezing). At the same time the significant difference between the group with wheezing of non -- RSV etiology and the control group was not observed. Decreasing of neopterin was significant in the II and III groups. IgE levels were elevated significantly in the second group of patients with recurrent wheezing. In this group negative correlation between neopterin and IgE was found.

Biomarkers↗
PubMed2006

Serum neopterin concentrations in healthy healthcare workers compared with healthy controls and patients with pulmonary tuberculosis.

BACKGROUND: The aim of this study was to compare serum neopterin levels in patients with active pulmonary tuberculosis, healthy healthcare workers who had close contact with patients, and healthy volunteers. All of the healthy volunteers stated that they had not encountered possible risk factors for exposure to Mycobacterium tuberculosis infection. MATERIAL/METHODS: Thirty-nine patients, 39 healthy healthcare workers, and a control group of 39 healthy volunteers who had no infection or other diseases were included in this study. Neopterin assay was performed in accordance with the manufacturer's instructions. RESULTS: Serum neopterin levels were 18.6+/-14.2 nmol/l in patients, 9.8+/-2.9 nmol/l in healthy healthcare workers, and 3.4+/-5.2 nmol/l in healthy volunteers. Serum neopterin levels in each group were significantly different from each other (p<0.01). CONCLUSIONS: Levels of neopterin in patients and healthy healthcare workers significantly differ from the levels in healthy controls. The higher serum neopterin levels in healthy healthcare workers may be attributed to latent Mycobacterium tuberculosis infection, but it does not seem to be used in the diagnosis of latent Mycobacterium tuberculosis infection alone. However, more experiences are needed.

Adult↗
PubMed1991

Neopterin as a marker for activated cell-mediated immunity: application in malignant disease.

A review is presented on studies concerning neopterin determination in patients with malignant neoplastic diseases. Neopterin is produced chiefly by human macrophages through their activation by T-cell-derived interferon gamma. In vivo, determinationof neopterin in various body fluids provides a convenient way to monitor early events that are involved in cell-mediated immune responses. In malignant neoplasia, elevation of neopterin concentrations in body fluids depends on tumor type. Within a given type of tumor, more advanced stages are generally associated with higher levels than early disease. In a variety of different tumor types and sites, a significantly poorer prognosis was associated with high pretherapeutic neopterin concentrations. This predictive value is independent of several possible confounders such as stage or therapy. During follow-up malignant disease, neopterin elevations may predict deterioration of the clinical status of the patients and thereby provide a valuable additional marker for monitoring such patients. Possible immunobiological implications of the results are discussed.

Biomarkers, Tumor↗
PubMed1990

Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment.

Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.

Biopterins↗
PubMed1990

[Value of neopterin as an oncologic laboratory parameter--observations in gynecologic tumors].

First experience is presented concerning the diagnostic utility of serum neopterin determinations in cancer care. The data refer to single measurements (198 sera) and follow-up studies (30 gynecological cases) of the neopterin level of patients suffering from bowel carcinomas, mammary carcinomas, and gynecological disorders. The outcome reveals that single values do not essentially add to the diagnostic result obtainable by conventional markers. Therefore, the consistent follow-up of the neopterin level is recommended. As exemplified for a series of gynecological patients, repeatedly elevated serum neopterin values after therapeutic intervention indicate a worse prognosis than values remaining within the physiological range. These conclusions need to be more firmly established by extended observation time and a greater number of cases. To make better and reliable use of neopterin in cancer diagnosis, it is necessary to analyse the immunological background of the altered neopterin synthesis (or shedding) in malignant diseases.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection.

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.

AIDS-Related Complex↗
PubMed1989

[Simple chromatographic determination of the neopterin marker in immunopathies].

Estimation of neopterin in urine has become part of examination in phenylketonuria, malignities, immunodeficiency incl. AIDS and HIV infection. The authors describe a simple chromatographic method for estimation of neopterin which does not call for highly efficient liquid chromatography nor imported kits. The di- and tetrahydro- forms of neopterin are oxidized with MnO2 and stable neopterin is obtained. The specimen is purified on a Dowex 50WX4 (Fluka) column in a H+ cycle and on PRESEPC18 (TESSEK) columns. Then thin-layer chromatography on Merck Kieselgel 60F254 plates is used in a system of ethyl acetate--isopropanol--1 N NH4OH (35:45:25). Fluorescence is assessed on a densitometer (Shimadzu CS-920 at 367.5 nm). The RF of neopterin is 0.214. The fluorescence is linear within the range of 5-200 ng. The method is sufficiently sensitive also for the estimation of normal neopterin excretion. The authors submit the results of estimations in controls, immunopathies and AIDS.

Acquired Immunodeficiency Syndrome↗