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PubMed2005

Mechanism of neopterin-induced myocardial dysfunction in the isolated perfused rat heart.

Neopterin is a sensitive marker for diseases involving increased activity of the cellular immune system in humans. Many studies, however, provide evidence for neopterin not only as a marker, but also for its characteristic effects. Recently, we were able to demonstrate a considerable influence of exogenous neopterin at a concentration of 100 mumol/l on cardiac performance in the Langendorff model of isolated perfused rat hearts. The present study was designed to investigate its possible mechanism. During co-infusion of neopterin at a concentration of 100 mumol/l with the unspecific nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate, the nitric oxide donor PAPA NONOate, the free radical scavenger N-acetylcysteine, or the pro-inflammatory cytokine tumor necrosis factor-alpha the effects on cardiac contractility parameters and coronary vascular resistance were studied in 67 male Sprague-Dawley rats. The temperature-controlled and pressure-constant Langendorff apparatus was used with retrograde perfusion of the aorta and a Krebs-Henseleit buffer. Neither the unspecific nitric oxide synthase inhibitor nor the nitric oxide donor excludes nitric oxide from playing a mechanistic role in our perfusion studies. Tumor necrosis factor-alpha was without any synergistic or antagonistic effects when co-treated with neopterin. N-acetylcysteine was most effective in abolishing neopterin-dependent effects on cardiac function. The negative effects of neopterin on cardiac performance might be due to an enhancement of oxidative stress by neopterin that can be attenuated by the antioxidant N-acetylcysteine. Neopterin has to be considered a pathogenic factor in the development of cardiac dysfunction in chronic disease states with high neopterin levels secondary to activation of the immune system.

Acetylcysteine↗
PubMed2000

Neopterin: a prognostic variable in operations for lung cancer.

BACKGROUND: We studied the prognostic value of preoperatively measured neopterin to predict survival of lung cancer patients. Neopterin is produced and secreted by interferon-gamma-stimulated monocytic cells. High urinary neopterin concentrations are found in patients with viral infections, allograft rejection episodes, and some malignant diseases. In various tumor types high urinary neopterin concentrations are associated with a worse prognosis. METHODS: Preoperative neopterin levels of 110 patients (29 women, 81 men) with lung cancer including 7 patients with small cell lung cancer were measured and related to the time of survival after operation. Patients with clinically suspected stage IIIB lung cancer were not operated and therefore not enrolled in this study. Infectious diseases were not apparent at the time of preoperative urine sampling. Median postoperative follow-up period was 17.4 months. RESULTS: In a univariate analysis, patients with a preoperative neopterin concentration of more than 212 micromol/mol creatinine (4th quartile) were determined to have a significantly lower survival probability. In a multivariate analysis, a neopterin concentration of more than 212 micromol/mol creatinine (p < 0.01) and T-stage status (p < 0.005) were determined to be significantly predictive variables for worse survival prognosis. CONCLUSIONS: Preoperative neopterin proved to be a reliable prognostic factor for survival. Immunology may provide an accurate assessment of tumor aggression and its clinical behavior. In this sense, neopterin can serve as an immunologically based estimation of malignant outgrowth. In patients who are operable by clinical tumor stage but have a high risk for operation, elevated preoperative neopterin may help in the decision for a nonoperative treatment.

Adult↗
PubMed1986

Assessment of plasma neopterin in clinical kidney transplantation.

Serial plasma samples of 172 kidney transplant recipients and 42 chronic dialysis patients were evaluated retrospectively in a radioimmunoassay to determine the clinical relevance of plasma neopterin levels. Dialysis patients had a higher neopterin level 196 +/- 82 nmol/L (mean +/- SD) than 70 healthy controls (7 +/- 4 nmol/L). In 45 patients with a completely uneventful postoperative course, elevated pretransplant neopterin levels dropped rapidly within a week to a mean of 30 nmol/L and remained stable thereafter. In 22 outpatients with stable graft function there was a highly significant correlation between 170 paired serum creatinine and plasma neopterin values (r = 0.94). A group of 13 patients had experienced delayed graft function (ATN) without rejection. Their one-week mean neopterin level was 100 nmol/L and continued to drop in parallel with the serum creatinine. Another 15 patients rejected their kidneys irreversibly within 3 weeks-6 of them had extremely high neopterin levels during the rejection process (range 500-1000 nmol/L) that were not seen in other patients. A total of 169 rejection episodes in 43 patients were treated with bolus-dose cortisone. On the day of bolus therapy, both serum creatinine (P less than 0.002) and neopterin (P less than 0.005) were elevated. At 24 hours prior to bolus cortisone therapy, creatinine levels were not significantly elevated, whereas there was a significant rise in plasma neopterin (P less than 0.01). The overall sensitivity of neopterin increase was 86% with a 17% probability of false positives, and the sensitivity was 95% in biopsy-proved rejections. Plasma neopterin appears to be a useful marker for early detection of rejection and for identifying severe rejections that are not responsive to treatment.

Biopterins↗
PubMedDate not supplied

Serum neopterin and activity of coronary artery disease.

Inflammation plays a key role in the pathogenesis of atherosclerosis. In coronary artery disease (CAD), the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall in patients with CAD. Macrophages activated by interferon gamma synthesize metalloproteinases and neopterin, a pteridin derivative that has been used as an immune marker. To determine neopterin levels in patients with chronic CAD and acute coronary syndromes, the authors studied 116 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age 68.5 +/- 14.3, range 40 to 86 years) with unstable angina or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7, range 47 to 83 years) with signs and symptoms of clinically stable CAD; and 3) 60 consecutive healthy blood donors (38 men, 22 women; mean age 54.4 +/- 6.23, range 44 to 66 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. In patients with unstable angina and AMI before thrombolytic therapy, neopterin levels were not significantly different from levels in patients with stable CAD (5.97 +/- 1.4 versus 7.84 +/- 3.56 nmol/L; P = 0.15). Neopterin levels in both patient groups did not significantly differ from levels in control subjects (P > 0.1). Neopterin levels in patients with unstable angina and AMI were measured four times during a 72-hour period. The lowest value was observed at baseline and differed significantly from values after 72 hours (P < 0.001; 5.97 +/- 1.4 versus 9.25 +/- 2.36). Neopterin levels after 72 hours were also significantly different from initial values in patients with stable CAD (P < 0.001). There was no correlation between neopterin and creatine kinase (CK) levels, CK-MB isoenzyme, or troponin I as markers for the extent of the myocardial injury during the observation period. These data do not support previous reports of higher baseline levels of serum neopterin in patients with unstable angina or AMI compared with patients with chronic, stable CAD and healthy controls. Neopterin as a marker of macrophage activation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 72 hours), supporting the hypothesis of monocyte and macrophage activation in patients with an acute coronary syndrome or AMI.

Adult↗
PubMed1994

Interferon-gamma stimulates neopterin release from cultured kidney epithelial cells.

The ability of cultured kidney epithelial cells (KEC) to secrete neopterin, which is a marker of the activation of immune system was studied. In this study interferon gamma (IFN-gamma) was shown to induce neopterin release from KEC in a dose- and time-dependent manner. Many other cytokines and mitogens (IL-1 beta, IL-2, IL-6, LPS and phorbol ester) were tested for their ability to induce neopterin in KEC but all failed to induce a significant release of neopterin from KEC. By itself TNF-alpha induced a release of small amounts of neopterin but strongly potentiated the effect of IFN-gamma in a synergistic manner to induce neopterin secretion. These data indicate that not only monocytes and macrophages which it is well known secrete neopterin, but KEC are responsible also for the high serum or urine level of neopterin observed in patients with kidney allograft rejection or infections episodes. As the amount of neopterin released by KEC is smaller than that secreted by activated macrophages, the contribution of KEC to the overall production of neopterin during certain diseases may be small.

Biopterins↗
PubMed1993

Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.

Adult↗
PubMedDate not supplied

Urinary neopterin in patients with liver tumors.

AIMS AND BACKGROUND: Primary and secondary liver tumors are associated with poor prognosis. Neopterin is an indicator of systemic immune activation, and increased neopterin concentrations have been associated with poor prognosis in a wide range of malignant tumors. METHODS: Urinary neopterin was determined by high-performance liquid chromatography in 154 patients with primary and secondary liver tumors. The survival of different groups of patients was compared by log-rank test, and Cox regression was used for multivariate analysis. RESULTS: Urinary neopterin was significantly increased in patients compared to controls. A statistically significant correlation was observed between urinary neopterin and age of the patients, hemoglobin concentration, mean erythrocyte volume and peripheral blood leukocyte or platelet count. In univariate analysis, urinary neopterin below 214 micromol/mol creatinine, peripheral blood leukocytes below 8 x 10(9)/L, hemoglobin equal to or above 125 g/L, no extrahepatic tumor, stage of liver involvement, and colorectal, breast or ovarian primary were significant prognostic factors for survival. In multivariate analysis, Bengtsson stage, presence of extrahepatic involvement, primary other than colorectal, breast or ovarian carcinoma, peripheral blood leukocyte count and urinary neopterin were independent prognostic factors. Increased urinary neopterin during and at the end of follow-up was also associated with poor prognosis. CONCLUSIONS: Urinary neopterin is increased in patients with liver tumors. Neopterin is an independent prognostic indicator in patients with liver tumors along with Bengtsson stage, presence of extrahepatic disease, primary site and peripheral blood leukocyte count.

Adult↗
PubMed1992

The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases.

The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.

Animals↗
PubMed1999

Levels of serum neopterin are increased in pancreatic cancer patients and correlate with the prognosis.

UNLABELLED: Neopterin has been recognized as a valid marker for cellular immune activation. Raised neopterin levels indicate the stimulation of macrophages and indirectly T-cell activation. So far no data is available on serum neopterin in pancreatic cancer patients. PATIENTS: In this prospective clinical study serum neopterin values were evaluated in 83 patients with adenocarcinoma of the pancreas (PC), 47 patients with chronic pancreatitis (CP), 8 patients with cystadenocarcinoma (CA) of the pancreas and 24 healthy controls (HC). RESULTS: Serum neopterin was significantly elevated in PC (p < 0. 05) and CA (p < 0.04) as compared to HC. There was no difference found between CP and HC. Pancreatic cancer patients with neopterin levels above 2 pmol/ml had a significantly better survival (p < 0. 05) regardless of stage. In stage III and IV (UICC) this difference was highly significant (p < 0.001). Serum levels of neopterin in resectable patients were also significantly correlated with increased survival and in multivariate analysis proved to be an independent prognostic factor. Neopterin in PC was neither correlated with sex, resectability nor with CA 19/9 and CEA. CONCLUSIONS: Patients suffering from PC who did show activated cellular immune response reflected in elevated neopterin levels above 2 pmol/ml had a significantly better prognosis regardless of tumor stage. In advanced stages elevated neopterin concentrations were significantly associated with increased survival. Cellular immune response seems to influence survival in these advanced stages to a higher degree as expected. These findings underline the possibility for supportive immunotherapy in this patient group.

Adult↗
PubMed1992

Monitoring of serum neopterin in renal transplant recipients.

Postoperative management of kidney allograft recipients requires a reliable and rapid diagnostic method so that proper therapy can be initiated. In this study, we tried to correlate serum neopterin levels with different conditions after transplantation. Serial serum neopterin levels were assessed after operation. Serum neopterin levels of uremic patients were significantly higher than those of healthy persons (239.9 +/- 177.7 nmole/L, n = 33 vs 6.14 +/- 2.78 nmole/L, n = 10, p < 0.001). In recipients with a stable post-transplant course, the serum neopterin level was low. On the contrary, acute rejection episodes were associated with a high level of serum neopterin which declined after successful treatment, although the difference was not significant (96.2 +/- 57.7 nmole/L vs 56 +/- 38.1 nmole/L, p > 0.05). The serum neopterin level was also high in post-transplant acute tubular necrosis (ATN, 256.6 nmole/L), which gradually declined parallel to the resolution of ATN. The neopterin level was low in patients with cyclosporine nephrotoxicity (17.8 +/- 7.6 nmole/L). In summary, the serum neopterin levels were persistently high in uremic and post-transplant ATN patients. Acute rejection episodes were correlated with an increased level of neopterin. It appears that daily measurement of the serum neopterin level may be useful for biochemical detection of immunologic complications in allograft recipients.

Adult↗
PubMed2006

[The role of serum neopterin level in the evaluation of activation and response to treatment in the patients with pulmonary tuberculosis].

Neopterin is an important parameter showing cell mediated immunity activation. In this study we aimed to determine whether serum neopterin level could be used as a marker in the evaluation of tuberculosis activation and response to treatment. The study comprised 40 new case smear positive pulmonary tuberculosis patients and 40 healthy control. Serum neopterin levels were measured both before the treatment and 2nd month of the treatment in the patient group. The association between serum neopterin level and clinical, radiological and bacteriological parameters were also investigated. In patients with pulmonary tuberculosis the mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and 21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients were significantly higher than the control group (p=0.001). Also, there was significant difference between serum neopterin levels before the treatment and the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the group with extensive disease than the cases with limited disease (p=0.02). In conclusion, we think that serum neopterin level might be used as a reliable immunological marker in the evaluation of tuberculosis activation and response to treatment.

Adolescent↗
PubMed1991

Clinical significance of serum and urinary neopterins in patients with chronic renal disease.

To determine the clinical significance of serum and urinary neopterins in patients with chronic renal disease, we measured these values using IMMUtest Neopterin RIA kits. Serum neopterin levels in patients with chronic glomerulonephritis (CGN) (10.2 +/- 8.1 nmol/l) and in those with chronic renal failure (CRF) (109 +/- 90) were significantly increased compared with the control subjects (C) (4.2 +/- 2.4) (p less than 0.001). The levels of serum neopterins in patients on chronic hemodialysis (HD) (212 +/- 106) were increased almost twofold compared with CRF (p less than 0.001). In CGN and CRF, a strong positive correlation was demonstrated between serum neopterin levels and serum creatinine concentrations (r = 0.95, p less than 0.001). In HD patients, neopterin levels and serum were not correlated with the length of time on dialysis. The urinary neopterin excretion ratios (urinary neopterin/urinary creatinine level) in CRF (227 +/- 114 mumols/molCr) were significantly increased compared with C (116 +/- 43) (p less than 0.01). A significantly negative correlation was observed between the urinary neopterin levels and the creatinine clearance in CGN and CRF (p less than 0.01). These data suggest that, in patients with chronic renal disease, the neopterin levels in serum are closely linked with glomerular filtration rate and yet the urinary neopterin/creatinine ratios may reflect the predominance of increased tubular secretion of neopterin over the renal injury per se.

Adult↗
PubMed1990

[Serum neopterin in dilated cardiomyopathy].

RIA was used to measure the level of neopterine and beta 2-microglobulin in the sera of 43 patients with a verified diagnosis of dilated cardiomyopathy (DCMP). In DCMP patients, the mean level of neopterine was 11.25 +/- 1.05 nM/l and was significantly higher than in donors (5.6 +/- 0.5 nM/l). The concentration of neopterine exceeding 9 nM/l was discovered in 55% of DCMP patients. The rise of neopterine concentration was particularly marked in patients with inflammatory reaction in the myocardium according to endomyocardial biopsy. In that patients' group, the mean level of neopterine was 12.9 +/- 2.02 nM/l while the rise of its concentration over 9 nM/l was recorded in 9 (81%) of 11 patients examined. The correlation was established between the rise of the concentration of neopterine and beta 2-microglobulin. In patients with the concentration of neopterine over 9 nM/l, the mean level of beta 2-microglobulin constituted 3.33 +/- 0.32 mg/l and in patients with the normal concentration of neopterine, it amounted to 1.91 +/- 0.18 mg/l. The growth of the concentration of beta 2-microglobulin in the groups of patients under comparison was seen in 79 and 14% of cases, respectively. It is concluded that neopterine measurements are advisable in the laboratory diagnosis of myocarditis in DCMP patients. Potential mechanisms of the rise of neopterine formation are discussed from the standpoint of hyperinterferonemia.

Adolescent↗
PubMed1989

Serum neopterin changes in HIV-infected subjects: indicator of significant pathology, CD4 T cell changes, and the development of AIDS.

Serum neopterin is a metabolite of dihydroneopterin triphosphate, which is produced from GTP during immune activation. A study was undertaken in homosexual male subjects followed at 6 month intervals for 3 or more years to determine the value of serum neopterin changes induced by HIV infection. The significance of serum neopterin levels in evaluating prognosis of HIV-infected individuals was also assessed. Serum neopterin was found to be a useful indicator of the presence of HIV infection. Stratification of 29 HIV seroconverters showed a strong inverse correlation between the serum neopterin rise and the blood CD4 T cell fall in the first year following HIV infection. Thus, a small increase in neopterin (less than 5 nmol/L) at the time of HIV seroconversion was associated with minimal CD4 T cell reduction and a large increase (greater than 12 nmol/L) was associated with a much greater CD4 T cell fall. Neopterin levels were markedly different (lower) in individuals with little or no CD4 T cell fall when compared with those with moderate or marked rates of T cell fall. This relationship between serum neopterin and the CD4 T cell level was further confirmed by an evaluation of both parameters in a group of 799 seropositive homosexual men. In this analysis, serum neopterin was shown to have a significant predictive value for the development of AIDS within 3 years. Furthermore, when serum neopterin and CD4 T cell measurements were considered together, the prognostic value of the combination was significantly greater than either alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches maximum levels early and late in the course of human immunodeficiency virus infection.

Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin (beta 2MG) reflect activation of the cellular immune response in the central nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients with human immunodeficiency virus (HIV) infection classified according to the Walter Reed staging system (WR)], neopterin and beta 2MG were determined in paired samples of CSF and serum. The permeability of the blood-CSF barrier and local release of neopterin and beta 2MG were taken into account: The molecular weight and diameter were used to determine filtration at the blood-CSF barrier. CSF neopterin levels were increased in all stages of HIV infection. beta 2MG levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l, P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l, P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75 +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of neopterin were markedly different in patients with HIV encephalopathy and toxoplasmosis (P less than 0.01). A high quantity of local release of the markers neopterin and beta 2MG may reflect HIV infection of the CNS in early and late stages and additional release upon opportunistic infections.

AIDS Dementia Complex↗
PubMed1983

Measurement of urinary neopterin in normal pregnant and non-pregnant women and in women with benign and malignant genital tract neoplasms.

Urinary neopterin was measured in healthy women (n = 209) and men (n = 208), in patients with benign gynecological tumors (n = 53), in women with precancerous lesions of the cervix and the endometrium (n = 24) and in women with cancer of the genital tract (n = 108). In addition urinary neopterin measurements were made in 109 pregnant women and 20 women in the puerperium. No significant difference was found between mean neopterin values in patients with benign gynecological tumors, in women with precancerous lesions and in healthy women. Patients with cancer had significantly higher mean urinary neopterin levels than the control group. Raised neopterin levels were found in 56% of patients with genital tract cancer, the figures varying between 93% for ovarian cancer and 47% for cancer of the cervix. Some of the cancer patients had serial urinary neopterin measurements and in about 80% there was some relation between urinary neopterin values and clinical progress as judged clinically and radiologically, the best agreement existing in patients with ovarian cancer. Significantly higher mean neopterin values were found during normal pregnancy and in the early puerperium than in non-pregnant healthy controls. Raised urinary neopterin excretion may be due to enhanced cell proliferation and alloantigenic activation of T-lymphocytes.

Adolescent↗
PubMed2003

Neopterin as a new biomarker for the evaluation of occupational exposure to silica.

OBJECTIVES: Silica is one of the most documented workplace contaminants. Long-term occupational exposure to silica is associated with an increased risk for respiratory diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease and lung cancer. Furthermore, a variety of immune-dysfunction-related diseases has been reported in silicotic individuals. Preliminary studies indicating enhanced levels of autoantibodies and several cytokines reflect an involvement of the immune system in the pathogenesis of silicosis and resulting complications. As an early and valuable biomarker of cellular immunity, neopterin is a low-molecular-mass compound belonging to the class of pteridines. It is produced by guanosine triphosphate via interferon-gamma, following the activation of T cells. The aim of the present study was to observe the alteration of neopterin in silica exposure, and also to show whether screening of neopterin levels may be of use for assessment of occupational exposure to silica. METHODS: In this study, serum and urinary neopterin levels, both in silica-exposed workers ( n=22) and healthy volunteers ( n=20), were investigated by ELISA, spectrophotometry and HPLC techniques. RESULTS: Serum neopterin levels of control and exposed groups were measured as 5.98+ or -0.44 and 7.86+ or -1.97 nmol/l, respectively ( P<0.05). Urinary neopterin levels were also increased in the exposed group: 97.60+ or -41.42 micromol/mol creatinine for controls and 165.59+/-78.20 micromol/mol creatinine for workers ( P<0.05). At the same time, the correlation between urinary neopterin levels, serum neopterin concentration and working years, smoking status, some complaints, and silica status in the working atmosphere were evaluated. CONCLUSIONS: Our findings suggest that the following up of neopterin levels may have diagnostic value in silica-related diseases such as silicosis. Moreover, its biological monitoring should be performed in workplaces for clinical diagnosis and prognosis.

Adult↗
PubMed1996

Effects of neopterin-derivatives on H2O2-induced luminol chemiluminescence: mechanistic aspects.

Neopterin, 6-D-erythro-1',2',3'-trihydroxypropyl-pterin, and its dihydroform, 7,8-dihydro-neopterin, are synthesized by human monocytes/macrophages upon stimulation by interferon-gamma. In the presence of iron chelator complexes neopterin enhances hydrogen peroxide-induced luminol chemiluminescence at neutral or slightly alkaline pH (7.5). In contrast, 7,8-dihydroneopterin scavenges chemiluminescence independently from the pH value and iron. In this study, we explored in more detail the mechanism possibly involved: analysis of the reaction products shows that 7,8-dihydroneopterin is oxidized and degraded to 7,8-dihydroxanthopterin and xanthopterin, whereas the neopterin molecule is not chemically altered during the chemiluminescence reaction. Investigations of the neopterin-induced effect show that mannitol, a scavenger of hydroxyl radicals, does not alter the enhancing effect of neopterin. L-histidine, which scavenges singlet oxygen almost as effective as hydroxyl radicals, reduces the enhancing effect of neopterin. However, singlet oxygen was not detectable during the reaction by measuring monomol light emission (1270 nm). When replacing hydrogen peroxide by 3-morpholinosydnonimine, a generator of hydroxyl radicals, or naphthalene-endoperoxide, a generator of singlet oxygen, in the luminol chemiluminescence assay, neopterin shows no enhancing effect irrespective of the presence of iron-(III)-EDTA. The data suggest that neopterin enhances hydrogen peroxide-induced luminol chemiluminescence in the presence of iron-(III)-EDTA by formation of a catalytic complex that seems to favor the formation of oxygen intermediates which derive from hydrogen peroxide and react with luminol.

Biopterins↗