Showing papers on "Neopterin published in 2009"

Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis

Abstract: Soluble tumour necrosis factor receptors (sTNF-Rs) play a role as modulators of the biological function of tumour necrosis factor-α (TNF-α) in an agonist/antagonist pattern. In various pathologic states the production and release of sTNF-Rs may mediate host response and determine the course and outcome of disease by interacting with TNF-α and competing with cell surface receptors. The determination of sTNF-Rs in body fluids such as plasma or serum is a new tool to gain information about immune processes and provides valuable insight into a variety of pathological conditions. Regarding its immediate clinical use, sTNF-Rs levels show high accuracy in the follow-up and prognosis of various diseases. In HIV infection and sepsis, sTNF-Rs concentrations strongly correlate with the clinical stage and the progression of disease and can be of predictive value. Determination of sTNF-Rs also gives useful information for monitoring cancer and autoimmune diseases. The information provided is often even superior to that obtained with classical disease markers, probably due to the direct involvement of the “TNF system” in the pathogenetic mechanisms in these patients. The available data imply that the measurement of sTNF-Rs, especially of the sTNF-R 75kD type, is a useful adjunct for quantification of the Th1-type immune response, similar to other immune activation markers such as neopterin and β2-microglobulin. Endogenous sTNF-Rs concentrations appear to reflect the activation state of the TNF-α/TNF receptor system.

Serum Immune Activation Markers Are Persistently Increased in Patients with HIV Infection after 6 Years of Antiretroviral Therapy despite Suppression of Viral Replication and Reconstitution of CD4+ T Cells

Abstract: The effect of long-term antiretroviral therapy on serum immune activation markers was assessed in a cohort of 63 patients before and after 6 years of boosted lopinavir-based antiretroviral therapy. High levels of most markers were associated with lower CD4(+) T cell counts at baseline and at year 6, with the exception of soluble cytotoxic T lymphocyte antigen-4 (sCTLA-4); high levels of sCTLA-4 were associated with higher CD4(+) T cell counts at year 6. Abnormalities of serum immune activation markers persisted after 6 years of ART but probably had different causes. Further investigation of the clinical usefulness of assaying immunoglobulin A, neopterin, and sCTLA-4 levels to assess the effectiveness of treatments for human immunodeficiency virus (HIV) disease are warranted.

The role of neopterin in atherogenesis and cardiovascular risk assessment.

Abstract: Neopterin is produced by human and primate monocyte/macrophages upon activation by pro-inflammatory stimuli like Th1-type cytokine interferon-gamma. Neopterin has pro-oxidative properties, which have been demonstrated in vitro in physicochemical and cell culture studies and also in in vivo experiments, e.g. the Langendorff perfusion model of rat hearts. In the past several years, the measurement of neopterin concentrations in body fluids including serum, urine and cerebrospinal fluid has revealed a potential role of this molecule in the prediction of long-term prognosis in both patients with cancer and those with systemic infections such as HIV-1 infection. Moreover, elevated neopterin concentrations have been reported in patients with coronary disease compared to controls and in recent years it has become apparent that increased neopterin concentrations are an independent marker for cardiovascular disease and a predictor of future cardiovascular events in patients with coronary artery disease. Current data suggest that the diagnostic performance of neopterin testing is comparable to that of well established biomarkers such as C-reactive protein and cholesterol plasma levels. The present article reviews the role of neopterin in the pathogenesis of cardiovascular disease and as a marker of coronary artery disease progression.

Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection

Abstract: The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-gamma, serum and urine neopterin, and beta 2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-gamma, neopterin and beta 2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-gamma-inhibiting erythropoiesis may be one underlying cause of anaemia in these patients.

Neopterin as a Predictor of Total and Cardiovascular Mortality in Individuals Undergoing Angiography in the Ludwigshafen Risk and Cardiovascular Health Study

Abstract: Background: Neopterin is produced upon activation of the cell-mediated immune response, and may be a novel risk marker for adverse outcomes resulting from coronary artery disease. Methods: We measured neopterin in 1801 study participants with and 511 without angiographic coronary artery disease. Rates of death were determined after a median follow-up of 8.0 years. Results: Estimated glomerular filtration rate and N-terminal pro-B–type natriuretic peptide (NT-proBNP) were the strongest predictors of neopterin. Neopterin was positively related to age and inversely related to LDL cholesterol, HDL cholesterol, and triglycerides. Use of lipid-lowering drugs lowered neopterin. Sex, body mass index, diabetes mellitus, hypertension, smoking status, Friesinger coronary score, and clinical instability at presentation were not associated with neopterin. Unlike C-reactive protein, neopterin was not increased in unstable angina pectoris, non–ST–elevation myocardial infarction, or ST-elevation myocardial infarction. In the third and fourth quartiles of neopterin, unadjusted hazard ratios for death from any cause were 1.94 (95% CI 1.44–2.61) and 3.32 (95% CI 2.53–4.30) compared to individuals in the first quartile, whereas hazard ratios for death from cardiovascular causes were 2.14 (95% CI 1.44–3.18) and 3.84 (95% CI 2.67–5.52), respectively. Neopterin remained predictive of total and cardiovascular mortality after adjusting for sex, age, body mass index, type 2 diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol, triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical status at presentation, but NT-proBNP substantially weakened this association. Conclusions: Neopterin is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease.

Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

Abstract: Aim Cerebrospinal fluid (CSF) neopterin production is increased by interferon-gamma stimulation and appears to act as a marker of intrathecal immune activation. We aimed to test the usefulness of elevated CSF neopterin as a biological marker of central nervous system (CNS) inflammation. Method We retrospectively reviewed CSF neopterin in 158 children (89 males, 69 females, mean age 4y 1mo, SD 3y 11mo, range 1mo–15y). Results CSF neopterin levels in children with chronic static CNS disorders (n=105) were predominantly low, suggesting that inflammation is rare in these patients. We created an upper value of normal (chronic static group 95th centile 27.4nmol/l). CSF neopterin was elevated in all 10 patients with acute encephalitis and in 10 of 12 patients with other acute inflammatory CNS disorders (demyelination, post-infectious ataxia, myelitis). CSF neopterin was also significantly elevated in patients with chronic progressive disorders of inflammatory origin. Interestingly, CSF neopterin was elevated in four of six patients with chronic static disorders who were tested during a febrile exacerbation of seizures or dystonia, suggesting that intrathecal immune activation may be important in this setting. Interpretation Neopterin has a short half-life and was useful for monitoring inflammation activity in a patient with relapsing–remitting encephalitis. CSF neopterin is a useful marker of inflammation in a broad range of acute and chronic CNS disorders, and is a significantly more sensitive marker of inflammation than CSF pleocytosis.

Correlation between neopterin, interferon-gamma and haemoglobin in patients with haematological disorders.

Abstract: In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.

Kynurenine metabolites and inflammation markers in depressed patients treated with fluoxetine or counselling

Abstract: SUMMARY 1 Depression could result from changes in tryptophan availability caused by activation of the kynurenine pathway as a result of inflammation. In the present study, we examined patients newly diagnosed with depression to determine whether kynurenines and related factors change in parallel with improvements in mood. 2 Concentrations of 5-hydroxytryptamine (5-HT; serotonin), 5-hydroxyindoleacetic acid (5-HIAA), oxidized tryptophan metabolites, brain-derived neurotrophic factor (BDNF) and inflammatory mediators (interleukin (IL)-2, C-reactive protein (CRP), neopterin) were measured in peripheral blood during an 18 week period of treatment with fluoxetine, fluoxetine plus tri-iodothyronine (T3) or psychiatric counselling. 3 The results showed significant improvements in mood, with reduced 5-HT concentrations in patients given fluoxetine and a rise in plasma tryptophan in patients given counselling or fluoxetine and T3. The addition of T3 to the fluoxetine regimen appeared to slow recovery from depression, although the use of T3 was associated with a fall in thyroxine concentrations. Changes in 5-HT concentrations did not correlate with psychiatric scores and were seen only in drug-treated groups, not those given counselling. There were no associated changes in absolute concentrations of kynurenines, BDNF, CRP, neopterin or IL-2. With fluoxetine treatment, there were correlations between the concentrations of kynurenine metabolites and the psychiatric rating scores, whereas no correlations were found with BDNF or inflammatory markers. 4 It is concluded that depression scores are largely independent of inflammatory status, but kynurenine metabolism may be related to the degree of depression after fluoxetine treatment.

Double-faced cell-mediated immunity in β-thalassemia major: stimulated phenotype versus suppressed activity

Abstract: In this study, the immunologic abnormalities of Iranian β-thalassemia major patients were characterized, considering their clinical parameters including splenectomy status and iron overload. Serum samples and peripheral blood mononuclear cells were collected from 28 patients and 30 age- and sex-matched healthy individuals. Patients with thalassemia showed significantly increased absolute lymphocyte counts compared with the control group. An increased number of activated T cells and higher levels of serum neopterin were also observed in thalassemia patients, which suggest chronic stimulation of immune system. On the contrary, T-cell proliferation and interleukin 2 (IL-2), interferon gamma (IFN-γ), and IL-4 production were suppressed in patients compared to controls. Patients with high serum ferritin levels produced significantly less IFN-γ and IL-2, indicating the immunosuppressive effect of iron overload in β-thalassemia patients. The serum levels of tumor necrosis factor alpha and absolute counts and percentages of B and T cells were higher in splenectomized patients; however, serum levels of neopterin significantly decreased in splenectomized patients compared to the non-splenectomized group. Taken together, T lymphocytes express activated phenotype in polytransfused β-thalassemia major patients, while T cell proliferation and effector function are significantly suppressed. Multiple blood transfusion and continuous immune stimulation could be responsible for making such a double-faced immune response.

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma.

Abstract: Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Persistent elevation of plasma osteopontin levels in HIV patients despite highly active antiretroviral therapy.

Abstract: In human immunodeficiency virus (HIV) infection, not only HIV itself but also systemic immune activation plays a role in the disease progression to acquired immune deficiency syndrome (AIDS). The systemic immune activation may be present even during highly active antiretroviral therapy (HAART). An increased expression of osteopontin, a proinflammatory cytokine, during HAART was reported in lymph nodes of HIV infected individuals. Osteopontin is also known to be involved in the pathogenesis of various HAART-induced diseases. Here, we measured osteopontin and other inflammatory markers such as neopterin and galectin-9 using serially collected plasma from patients with HIV/AIDS to find novel markers for immune activation. Four AIDS patients complicated with various opportunistic infections and one acute HIV patient were studied. Osteopontin levels (normal levels: 130 pg/ml), with the exceptionally high level in the acute HIV patient (4,196 pg/ml). Neopterin levels (normal ranges: 2-8 pmol/L) were elevated in four patients (21-99 pmol/L). After HAART, the levels of galectin-9 and neopterin apparently decreased, whereas the levels of osteopontin did not decrease. Thus, the high levels of osteopontin were sustained despite the clinical improvement. Fisher exact probability test showed that the mode of the changes was different between osteopontin and galectin-9, and between osteopontin and neopterin (p = 0.024). We therefore propose that the plasma osteopontin is a useful marker of immune activation during HAART and HAART-induced side effects.

Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma

Abstract: Background: To explore the biological activity of EMD 273063 (hu14.18-IL2), a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2), in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood. Methods: Nine patients were treated with 4 mg/m2 per day of EMD 273063 given as a 4-h intravenous infusion on days 1, 2, and 3 every four weeks (one cycle). Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R), IL10, IL6, tumor necrosis factor alpha and neopterin. Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry. Results: Treatment was generally well tolerated and there were no study drug-related grade 4 adverse events. Grade 3 events were mainly those associated with IL2, most commonly rigors (3 patients) and pyrexia (2 patients). Best response on therapy was stable disease in 2 patients. There were no objective tumor regressions by standard response criteria. Systemic immune activation was demonstrated by increases in serum levels of sIL2R, IL10, and neopterin. There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site.

Association between the activation of macrophages, changes of iron metabolism and the degree of anaemia in patients with malignant disorders

Abstract: In this study, we investigated a possible association between the degree of macrophage activation - as measured by serum neopterin concentrations - and disturbances of iron metabolism, determined by the concentrations of ferritin and serum iron, in patients with malignant disorders. Additionally we evaluated correlations between these factors and the degree and type of anaemia. Seventy-three patients, who suffered from non-Hodgkin's lymphoma (NHL) (n = 43), Hodgkin's disease (n = 11), myeloma or monoclonal gammopathy of unknown significance (n = 9), myelodysplastic syndrome (n = 1), and solid tumours (n = 9), were examined. Mean neopterin levels were raised in all groups, patients with NHL showing the highest concentrations. Ferritin but not neopterin concentrations were higher in males than in females. A significant correlation was found between neopterin and ferritin concentrations (p less than 0.01). Considering only female patients the strength of the correlation was the same (p less than 0.02). In addition, we found inverse correlations of neopterin with haemoglobin and iron concentrations (all p less than 0.01). Similar relationships existed in patients during follow-up. Our results support the hypothesis of an association between the degree of activation of macrophages and the development of anaemia by a shift or iron towards the storage sites.

Elevated systemic IL-18 and neopterin levels are associated with posttraumatic complications among patients with multiple injuries: a prospective cohort study.

Abstract: Abstarct Introduction Posttraumatic systemic inflammatory response syndrome (SIRS), sepsis and their subsequent complication, the multiple-organ dysfunction syndrome (MODS), remain major complications following polytrauma. This prospective clinical study aimed at evaluating the association between these and plasma interleukin-18 (IL-18) and neopterin levels. Methods Inclusion in the series required an Injury Severity Score (ISS) >16, age 16–65 years, admission within 6 h of the accident and survival >48 h; 55 patients were enrolled. Over 14 days, plasma neopterin and IL-18 levels and the clinical course regarding MODS, SIRS and sepsis were recorded daily using the Marshall Score for MODS and the ACCP/SCCM criteria for SIRS and sepsis. Results Neopterin and IL-18 plasma levels were increased in +MODS cases as compared with −MODS cases over almost the entire observation period. IL-18 concentrations over days 3–6 were significantly increased among participants with sepsis. These increases were all apparent 2–3 days before the clinical diagnosis of sepsis or MODS was made. In contrast, no significant differences in neopterin and IL-18 plasma levels were observed between participants with and without SIRS. Conclusions Determinations of neopterin and IL-18 concentrations might represent early markers for posttraumatic complications such as MODS and sepsis. They might help to differentiate between SIRS and sepsis and thereby guide the timing of the surgery for polytrauma. Neopterin and IL-18 levels should be used together with the clinical status and other inflammatory markers (IL-6, IL-8, etc.) for prediction of posttraumatic complications.

Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors.

Abstract: Immune dysfunction in trauma patients is associated with immune system activation and inflammation. The cytokine-inducible enzyme IDO (indoleamine 2,3-dioxygenase) initiates the degradation of the essential aromatic amino acid tryptophan via the kynurenine pathway and could contribute to deficient immune responsiveness. Activated IDO is indicated by an increased kyn/trp (kynurenine/tryptophan) ratio. The aim of the present study was to investigate whether tryptophan degradation is associated with outcome in patients post-trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12-14 days of follow-up. Up to five samples within this observation period from each patient were included in this analysis, and a total a 69 samples were available. For further comparisons, concentrations of the immune activation marker neopterin were measured. Compared with healthy controls, the average kyn/trp ratio and kynurenine concentrations were increased in patients, whereas tryptophan concentrations were decreased. During follow-up, increased kyn/trp ratio and kynurenine concentrations (all P < 0.001) were observed, whereas the changes in tryptophan concentrations were not significant. Non-survivors had higher kyn/trp ratios and kynurenine concentrations compared with survivors. The kyn/trp ratio correlated with neopterin concentrations (r s = 0.590, P < 0.001). In conclusion, these results imply that increased tryptophan degradation in patients is due to activated IDO, which most probably is a consequence of a host defence response. These findings support a possible role for IDO in the development of immunodeficiency and death in patients.

Alterations in L-arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria.

Abstract: Low-grade inflammation is closely involved in the pathogenesis of type 2 diabetes and associated micro- and macrovascular complications. The nitric oxide (NO) precursor l-arginine, is relevant to diverse pathological conditions including type 2 diabetes and its complications. High sensitive-CRP (hs-CRP), neopterin and arginine levels were measured in 46 normoalbuminuric, 45 microalbuminuric type 2 diabetics and in 32 healthy controls in order to assess the relationship between markers of inflammation and l-arginine. Hs-CRP concentrations were higher in microalbuminuric diabetic patients compared to normoalbuminuric patients and controls. Diabetics had higher serum and urine neopterin levels than controls. Urine neopterin and l-arginine levels differed significantly among diabetic patients with and without microalbuminuria. There were significant positive correlations between hs-CRP and BMI in healthy controls and diabetics with and without microalbuminuria. In microalbuminuric diabetics, hs-CRP correlated with microalbuminuria (MAU). Significant predictors for the development of microalbuminuria were higher postprandial glucose levels, lower creatinine clearance and lower serum l-arginine levels. Assessment of early markers of inflammation and endothelial function, such as neopterin and NO precursor l-arginine, may help to predict incipient nephropathy more accurately in type 2 diabetic patients.

Effects of neopterin and 7,8-dihydroneopterin on hypoxia-induced renal erythropoietin production.

Abstract: Activation of the human cellular immune system is associated with greatly increased formation of the pteridines neopterin and 7,8-dihydroneopterin. It has been postulated that pteridines play a role in the pathogenesis of the anaemia of inflammation. Herein, we studied effects of pteridines on renal function, primarily on the synthesis of erythropoietin (Epo). The experiments were performed with isolated rat kidneys which were perfused hypoxically (pO 2 26 mmHg) at constant pressure (100 mmHg) in a serum-free recirculation system for 3 h. The results show that the rate of the production of Epo was significantly lowered when neopterin or 7,8-dihydroneopterin were added to the perfusate. Neopterin (200 μM) also reduced the renal Epo mRNA level. Both pteridines increased renal vascular resistance. 7,8-Dihydroneopterin lowered urine flow and glomerular filtration rate more potently than neopterin. Renal O 2 consumption and parameters of exocrine renal function (fractional reabsorption rates of sodium, glucose and water) were not altered by the pteridines, while the glomerular permeability was greatly increased. These results suggest that activated macrophages may not only inhibit the synthesis of Epo by generating cytokines and reactive O 2 species but also by the release of pteridines. In vivo, high concentrations of pteridines in renal tissue may aggravate the anaemia of inflammation.

Evaluation of some markers of subclinical atherosclerosis in Egyptian young adult males with abdominal obesity.

Abstract: Young adults with abdominal obesity are liable to have subclinical atherosclerosis that may contribute to an increased risk of cardiovascular disease later in life. This study aims to evaluate subclinical atherosclerosis and its possible correlation with some inflammatory and biochemical markers in Egyptian young adult males with abdominal obesity. The study includes 50 young adult males (age range: 19-29 years) divided into two groups. Group 1 comprises 20 non-obese subjects (controls). Group 2 comprises 30 apparently healthy obese subjects. Carotid intima media thickness (carotid-IMT) was estimated using B-mode ultrasonography of the common carotid arteries, and abdominal ultrasonography was performed to assess the presence of a fatty liver. Laboratory investigations included fasting levels of serum glucose, triglycerides (TG), cholesterol (total [TC], high-density [HDL-cholesterol] and low-density [LDL-cholesterol] lipoprotein fractions), high-sensitivity C-reactive protein (hs-CRP), neopterin, lipoprotein-a (Lp[a]), gamma glutamyl transferase (GGT), aspartate and alanine aminotransferases (AST, ALT), plasma plasminogen and fibrinogen. Results showed that carotid IMT, serum hs-CRP, neopterin, Lp(a), fibrinogen, plasminogen, TC, TG, LDL-cholesterol and liver enzymes were significantly elevated (P<0.001) in the obese group compared to controls. All obese subjects showed evidence of fatty liver. A significant positive correlation was found between carotid-IMT and body mass index, waist circumference, waist/hip ratio, cholesterol, triglycerides, neopterin, hs-CRP AST, ALT and GGT. Elevated serum levels of inflammatory biomarkers and increased ALT, AST and GGT, and non-alcoholic fatty liver disease biomarkers may be useful predictors of subclinical atherosclerosis.

Increased serum neopterin concentration as indicator of disease severity and poor survival in multiple myeloma.

Abstract: In this study we investigated serum neopterin levels in 73 multiple myeloma (MM) patients (63 determinations at diagnosis, 58 in remission, and 35 at relapse), in 56 monoclonal gammopathies of undetermined significance (MGUS), and in 70 normal controls. Median neopterin level was 5.3 nmol/l in normal controls, 6.8 nmol/l in MGUS, and 10.7 nmol/l in MM patients. In comparison to healthy subjects, significantly higher levels were observed in MM patients (p less than 0.0001). A statistical difference was observed between MGUS and MM patients at diagnosis (p less than 0.007). Compared to diagnosis, a further increase was noticed during relapse, suggesting a correlation between neopterin and disease activity. The prognostic significance of raised neopterin levels was confirmed by a survival analysis. Median survival for patients with high values was 20 months, whereas it was 63.9 months for those with low values (log-rank test p less than 0.003). Serum neopterin concentrations also correlated to beta 2 microglobulin levels and the percentage of CD38+ circulating lymphocytes, indicating a link between neopterin and other myeloma prognostic factors.

Procalcitonin, neopterin and C-reactive protein in diagnostics of intrauterine infection and preterm delivery.

Abstract: Objective The purpose of this study was to find out whether Procalcitoni, Neopterin and C-reactive protein are sensitive and specific markers of intrauterine infection. Methods We evaluated 155 patients from 26. to 41. week of pregnancy at the time of delivery. We measured serum concentrations of procalcitonin (PCT), neopterin and C-reactive protein (CRP) from mother's blood sample at the beginning of delivery and from umbilical cord blood after delivery. Results In first group occurred in higher percentage (27.41%) preterm delivery (26.-37. week of pregnancy), chorioamnionitis confirmed by histological examination (16.12%) and preterm premature rupture of membranes (24.19%). In this group occured perinatal infection of newborn in 61.29%. In the second group preterm delivery (6.31%) and perinatal infection of newborn (7.36%) occured in lower percentage. Conclusion The results suggest that the simultaneous measurement of CRP, PCT and NPT in mother's blood sample before delivery and umbilical cord blood may provide an accurate early diagnosis of infection and then preterm delivery (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.