Neopterin Levels and Indoleamine 2,3-Dioxygenase Activity as Biomarkers of Immune System Activation and Childhood Allergic Diseases

BACKGROUND: Although Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity. METHODS: We divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis. RESULTS: Neopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls (P < 0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols (P < 0.05). CONCLUSIONS: The Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.

Biochemical Analysis of Three Biological Fluids and its Response to Non-Surgical Periodontal Therapy in Pre and Postmenopausal Women with Periodontitis

OBJECTIVES: Periodontitis is a common chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. The stages of menopause also worsen inflammatory condition. Biomarkers from biological fluids can be used as a diagnostic indicator to correlate these two conditions of present and future disease activity. The aim of the present study was to evaluate the neopterin levels in three biological fluids obtained from pre- and postmenopausal women with periodontitis following non-surgical periodontal therapy (NSPT, that is, scaling).METHODS: This was a cross-sectional interventional study. Thirty women, aged 40–60 years, with periodontitis were selected according to their menstrual history. They were divided into the pre- and postmenopausal groups, with each group including 15 participants. The neopterin levels were measured in both groups at baseline and 3 months after NSPT. Intergroup comparison and percentage decrement analysis were performed using the independent sample t test, and intragroup comparison was performed using the paired t test.RESULTS: There were statistically significant reductions in the mean values of saliva, urine, and plasma from baseline to 3 months after NSPT in the groups. Intergroup comparison showed no significant values in the postmenopausal group, and a significant reduction was seen in the mean values was seen in the mean values.CONCLUSIONS: Neopterin levels decreased at 3 months after NSPT in both the groups, suggesting that NSPT can be a gold standard therapy and that the neopterin level could be a indicator to identify periodontal destruction.

The effect of periodontal therapy on neopterin and vascular cell adhesion molecule-1 levels in chronic periodontitis patients with and without acute myocardial infarction: a case-control study

Abstract The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. Objectives This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Material and methods Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. Results The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Conclusions Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.

Comparative Evaluation of Salivary Neopterin Levels and Its Effects to Periodontal Therapy in Pre- and Post-Menopausal Women

OBJECTIVES: Neopterin is a valuable diagnostic biomarker, which is elevated in inflammatory conditions like periodontitis, that is characterized by destruction of the supporting structures of the teeth. Among the biomarkers, neopterin occurs in body fluids, and acts as a diagnostic marker for present and future disease activity. METHODS: Thirty female subjects with chronic periodontitis, mean age 50 years (40-60 years) were included in this study. Depending upon their menstrual history, subjects were categorized into two groups of fifteen each. Group I 15 pre-menopausal women, and Group II 15 post-menopausal women. Saliva was collected, and neopterin levels were assessed by enzyme-linked immunosorbent assay in both the groups, at base line and after three months of nonsurgical periodontal therapy (NSPT). Periodontal parameters like pocket probing depth (PD) and Russell's periodontal disease index (PDI) were assessed before treatment as well as after three months of scaling and root planning. RESULTS: Intra group analysis showed significant markdown in the mean values of all the parameters from baseline to three months (P < 0.001), for all patients. The intergroup comparison, from baseline to 3 months also showed no significant change in PD and PDI values, but there was a statistically significant difference in the salivary neopterin levels (P = 0.04). CONCLUSIONS: Neopterin levels were found to be reduced in three months after NSPT in both the groups, suggesting that the NSPT is the gold standard therapy, and also that neopterin levels in saliva can be used as an indicator to identify periodontal inflammation and destruction.

Clinical and laboratory features of HTLV-I asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis from the Brazilian Amazon

ABSTRACT Clinical and laboratory parameters including blood and cerebrospinal fluid (CSF) neopterin were investigated in human-T-lymphotropic-virus-type-I associated-myelopathy/tropical-spastic-paraparesis-HAM/TSP and in HTLV-I carriers. HAM/TSP (n = 11, 2 males/9 females, median age = 48 years), recently diagnosed HTLV-I carriers (n = 21, 15 females/6 males, median age = 44 years), healthy individuals (n = 20, 10 males/10 females, median age = 34.6 years) from the Brazilian Amazon (Manaus, Amazonas State) were investigated. Neopterin was measured (IBL ELISA Neopterin, Germany) in serum samples of all the participants, in CSF of 9 HAM/TSP patients as well as in 6 carriers. In HAM/TSP patients, CSF cell counts, protein and glucose were measured, the Osame’s motor-disability-score/OMDS was determined, and brain/spinal cord magnetic-resonance-imaging (MRI) was performed. HAM/TSP patients had normal CSF glucose, leukocyte counts; and normal protein levels predominated. Brain-MRI showed white-matter lesions in 7 out of 11 HAM/TSP patients. OMDS varied from 2-8: 9 were able to walk, 2 were wheel-chair-users. The median serum neopterin concentration in HAM/TSP patients was 6.6 nmol/ L; min. 2.8- max. 12.5 nmol/ L); was lower in carriers (4.3 nmol/L; min. 2.7- max. 7.2 nmol/ L) as well as in healthy participants (4.7 nmol/ L; min. 2.7- max. 8.0 nmol/ L) (p < 0.05). CSF neopterin concentrations in HAM/TSP patients were higher than in serum samples, and higher compared to carriers (p < 0.05). Carriers had similar serum-CSF neopterin concentrations compared to healthy participants. Variable clinical and laboratory profiles were seen in HAM/TSP patients, however our results support the neopterin measurement as a potential biomarker of disease activity.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity / Associação de neopterina como marcador de ativação do sistema imunológico e atividade da artrite reumatoide juvenil

OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p < 0.05). A statistically significant higher mean level serum neopterin concentration (p < 0.05) was found in JIA patients (20.43 ± 8.73 nmol/L) than in controls (6.88 ± 2.87 nmol/L) (p < 0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-a, IL-6, MCP-1, and JADAS-27 (p < 0.05). No correlation was found between serum neopterin and CRP (p > 0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05).CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

OBJETIVO: Avaliar as concentrações plasmáticas de neopterina em pacientes com artrite idiopática juvenil (AIJ) ativa e correlacioná-las com a atividade da doença.MÉTODOS: Foram recrutados da clínica de Alergia e Imunologia Infantil da Universidade Ain Shams 60 pacientes diagnosticados com AIJ ativa, bem como 60 crianças aparentemente saudáveis com a mesma idade e o mesmo sexo no grupo de controle. A atividade da doença foi avaliada pelo Escore de Atividade da Doença da Artrite Juvenil em 27 Articulações (JADAS-27). Foram feitas investigações laboratoriais em todos os pacientes, incluindo a determinação da concentração de hemoglobinas, a taxa de sedimentação de eritrócitos e a proteína C-reativa. Foram mensuradas as concentrações séricas do fator de necrose tumoral alfa, interleucina-6 e proteína quimiotática de monócitos-1 e neopterina.RESULTADOS: Foi encontrada uma diferença significativa entre os pacientes com AIJ e os controles quanto às médias de Hb, TSE, FNT-a, IL-6 e MCP-1 (p < 0,05). Foi encontrado um nível estatística e significativamente maior de concentração média de neopterina sérica (p < 0,05) em pacientes com AIJ (valor médio de 20,43 ± 8,73 nmol/L) do que em controles (valor médio de 6,88 ± 2,87 nmol/L) (p < 0,05). Foram detectadas correlações positivas significativas entre a neopterina sérica e TSE, FNT-a, IL-6, MCP-1 e JADAS-27 (p < 0,05). Não foi encontrada correlação entre a neopterina sérica e a PCR (p > 0,05). A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05).CONCLUSÃO: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ.

Estimation of salivary neopterin in chronic periodontitis.

Background: Periodontal diseases are the most common bacterial infection predominantly associated with Gram‑negative microorganisms that exist in the subgingival biofilm. Analysis of saliva provides a noninvasive means of evaluating the role of the host response in periodontal disease. Though salivary enzymes can be used as the biomarkers, neopterin has been recently used as one of the important diagnostic tools in the field of periodontics. Hence, we aimed to identify the neopterin levels in unsimulated saliva from the chronic periodontitis patients and compare them with the periodontally healthy subjects. Materials and Methods: Twenty subjects participated in the study and were categorized as the experimental group (chronic periodontitis patients) and control groups (healthy subjects). Unstimulated saliva samples were collected from both the groups for neopterin estimation. Neopterin in saliva was estimated using Shimadzu High Performance Liquid Chromatography with LC‑20AD pump system, equipped with RF‑10 AXL fluorescence detector. Statistical Analysis Used: Data were expressed as mean ± SD and analyzed using GraphPad Prism version 6.0 (California, USA). Statistical analysis was done by Student’s t‑test Results: The neopterin level in unstimulated saliva was found to be higher in the experimental group than the control group with P ≤ 0.05. Conclusions: The chronic periodontitis patients showed higher neopterin level in unstimulated saliva as compared to control. Hence, neopterin can be used as a potential biomarker for identification of the periodontal disease in its initial stage can help in preventing the disease progression.

Effects of general and spinal anesthetic techniques on endothelial adhesion molecules in cesarean section / 대한마취과학회지

BACKGROUND: The aim of this study was to investigate the effects of anesthetic techniques used during general anesthesia (GA) and spinal anesthesia (SA) on endothelial adhesion molecules in the fetal circulation of healthy parturients undergoing elective cesarean section. METHODS: Patients were randomly assigned to either the general anesthesia (n = 20) or spinal anesthesia (n = 20) group. Maternal and cord blood neopterin, sE-selectin, and sL-selectin levels were measured in both groups. RESULTS: Cord blood neopterin concentrations in the SA group were not different from those in the GA group, but maternal neopterin levels in the SA group were different from those in the GA group. Maternal blood levels of sE-selectin and sL-selectin were not different between the two groups. Similarly, the cord blood levels of sE-selectin and sL-selectin were not different between the two groups. We found an increased inflammatory process in the fetal circulation depending on the anesthetic method used. CONCLUSIONS: These results indicate the effects of general and spinal anesthetic techniques on serum sL-selectin, sE-selectin, and neopterin levels in neonates and parturients undergoing elective cesarean section. sE-selectin and neopterin concentrations and leukocyte counts were higher in the fetal circulation than in the maternal circulation during both GA and SA.

Diagnostic values of neopterin and S100b for central nervous system infections in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the diagnostic values of cerebrospinal concentrations of neopterin (NPT) and S100b for central nervous system infections in children.</p><p><b>METHODS</b>Enzyme-linked immunosorbent assay was used to determinate the cerebrospinal concentrations of NPT and S100b in children with central nervous system infections and control children. The two groups of children were compared in terms of the two indicators, and the diagnostic values of the two indicators were evaluated by ROC curve analysis.</p><p><b>RESULTS</b>Children with viral encephalitis had significantly increased cerebrospinal concentrations of NPT and S100b compared with the control group and children with purulent meningitis (P<0.01); there was no difference in the cerebrospinal concentration of NPT between children with purulent meningitis and the control group, while the concentration of S100b in the purulent meningitis group was significantly higher than in the control group (P<0.01). According to the ROC curves, S100b was more valuable than NPT in the diagnosis of viral encephalitis; when cerebrospinal concentration was more than 0.384 ng/mL, S100b had a sensitivity of 93.3% and a specificity of 97.9%; a combination of the two indicators had a higher diagnostic value for viral encephalitis, with a sensitivity of 96.7% and a specificity of 97.9%.</p><p><b>CONCLUSIONS</b>Both NPT and S100b have certain values in the diagnosis of central nervous system infections in children, and S100b is better than NPT.</p>

Detection of serum neopterin in patients with hemophagocytic lymphohistiocytosis and its significance / 中国实验血液学杂志

This study was aimed to detect the peripheral blood serum neopterin (Npt) level in the patients with hemophagocytic lymphohistiocytosis (HLH) and to explore its significance in HLH. The enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum Npt level and sCD25 level in 20 HLH patients before and after treatment and 15 healthy controls. The results indicated that the serum Npt and sCD25 levels in HLH patients were significantly higher than those in healthy controls (P < 0.0001). The serum Npt and sCD25 levels in the HLH group decreased significantly after treatment, respectively (P < 0.0001). The correlation analysis of Npt with sCD25 before and after treatment showed that they had significant correlation (r = 0.81, P < 0.05 before treatment; r = 0.65, P < 0.05 after treatment). Meanwhile, the level of serum Npt and ferritin had a significant correlation in newly diagnosed HLH patients (r = 0.55, P < 0.05). It is concluded that the serum Npt may play an important role in the HLH pathogenesis, the enhancement of Npt levels has an important significance for diagnosis and evaluation for HLH.

Effects of fuzheng paidu tablet on tumor necrosis factor-alpha and neopterin of thirty-two asymptomatic HIV carriers / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Fuzheng Paidu Tablet (FPT) on serum levels of tumor necrosis factor-alpha (TNF-alpha) and neopterin (NPI) in patients with asymptomatic human immunodeficiency virus (HIV) carriers.</p><p><b>METHODS</b>Using flow cytometry detection technology, CD T lymphocyte in anticoagulant blood sample of 32 asymptomatic HIV infection patients who were taking FPT for 6 months was detected and compared with before treatment. The serum levels of TNF-alpha and NPI were determined using ELISA method and compared with 22 healthy volunteers.</p><p><b>RESULTS</b>After 6 months of treatment by FPT, the CD4+ T lymphocyte of asymptomatic HIV carriers increased from (368.63 +/- 111.54)/mm3 to (412.72 +/- 159.63)/mm3. Before treatment the serum levels of TNF-alpha [(20.05 +/- 13.08) nmol/L] and NPI [(9.55 +/- 2.52) nmol/L] were obviously higher than those of the healthy volunteers [(12.20 +/- 4.07) nmol/L and (5.91 +/- 1.43) nmol/L] (P < 0.05). After 6 months of treatment by FPT, they were lower after treatment than before treatment (P < 0.05). But there was no statistical difference in the serum TNF-alpha level [(11.06 +/- 4.71) nmol/L] when compared with the healthy volunteers group (P > 0.05). But the serum NPI level [(8.08 +/- 2.13) nmol/L] was still higher than that of the healthy volunteers group (P < 0.05).</p><p><b>CONCLUSIONS</b>One of the pathological factors for asymptomatic HIV infection is abnormal immune activation represented by increased serum levels of TNF-alpha and NPI. FPT could lower the serum levels of TNF-alpha and NPI in asymptomatic HIV infection patients, which was one of its possible mechanisms for its efficacy.</p>

Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease

PURPOSE: We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core. CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.

Circadian blood pressure variability and plasma neopterin level before and after surgery for obstructive sleep apnea syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the change of circadian blood pressure variability (BPV) and plasma neopterin before and after surgery (uvulopalatopharyngoplasty) for patients with obstructive sleep apnea syndrome (OSAS).</p><p><b>METHODS</b>A total of 382 OSAS patients underwent uvulopalatopharyngoplasty were divided into three groups based on polysomnography (PSG) results: mild OSAS (n = 206), moderate OSAS (n = 108) and severe OSAS (n = 68). Plasma neopterin, 24-hour ambulatory blood pressure monitoring (ABPM), PSG were measured before and 3 months after surgery.</p><p><b>RESULTS</b>Plasma neopterin increased in proportion to severity of OSAS before surgery (15.08 nmol/L, 27.68 nmol/L and 37.32 nmol/L in patients with mild to severe OSAS) which were significantly reduced post surgery (9.92 ng/ml, 15.07 ng/ml and 18.54 ng/ml, all P < 0.05 vs. pre-surgery). The incidence of non-dipper curve in three OSAS groups were 50.2%, 72.7% and 86.5%, respectively before surgery and the values decreased to 34.8%, 48.2% and 49.2% after surgery (all P < 0.05 vs. pre-surgery). Relevance analysis indicates that D-value of nocturnal and diurnal blood pressure was negatively correlated with plasma neopterin.</p><p><b>CONCLUSION</b>Our findings indicated that plasma neopterin and the incidence of non-dipper could reliably reflect OSAS severity and could thus be used to evaluate the surgery efficacy. Plasma neopterin might be an important player in the pathophysiology of OSAS via modulating blood pressure variability.</p>

Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection

BACKGROUND: Fever as a common presenting complaint in pediatric patients can be due to various causes. Differentiating bacterial infection from other causes is important because the prompt use of antibiotics is critical in bacterial infection. Traditional markers of infection such as BT and WBC count may be unspecific and culture may be late or absent. CRP and Procalcitonin (PCT) have been considered to evaluate the evolution of infections and sepsis in patients presenting with SIRS. Neopterin has also been proposed to aid in the diagnosis of bacterial infection. In this study, we compared the value of the serum PCT, neopterin level, and WBC count for predicting bacterial infection and outcome in children with fever. METHODS: 158 pediatric (2-120-month-old) patients suspected to have acute bacterial infection, based on clinical judgment in which other causes of SIRS were ruled out were included in the study. WBC count with differential was determined and PCT and neopterin levels were measured. RESULTS: PCT level was higher in bacterial infection and patients who were complicated or expired. CONCLUSION: Rapid PCT test is superior to neopterin and WBC count for anticipating bacterial infection, especially in ED where prompt decision making is critical. ABBREVIATIONS: BT, body temperature; WBC, white blood cell; PCT, procalcitonin; CRP, C-reactive protein; SIRS, systemic inflammatory response syndrome; ED, emergency department.

Incomplete immunological recovery following anti-tuberculosis.

Background & objectives: Mycobacterium tuberculosis infection has been shown to result in increased HIV replication and disease progression in HIV-infected individuals through increased immune activation. The objective of this study was to correlate plasma levels of immune activation markers with the presence of tuberculosis (TB) in HIV-infected and uninfected individuals, and to study the changes following anti-tuberculosis treatment. Methods: Plasma markers of immune activation - neopterin, beta-2-microglobulin (β2M) and soluble tumour necrosis factor alpha receptor type I (sTNFα-RI) were measured by ELISA in 42 HIV positive TB patients (HIV+TB+) undergoing a six-month course of TB chemotherapy. Thirty seven HIV+ persons without active TB, 38 TB patients without HIV infection, and 62 healthy volunteers served as controls. Results: Plasma levels of all three markers were elevated in HIV+ individuals, more so in those with active TB. When HIV+ individuals were further categorized based on CD4+ T cell counts, HIV+TB+ patients with CD4+ T cells counts < 200 cells/μl were found to have the highest levels at baseline with a steep fall in neopterin and sTNFα-RI during treatment, but in most instances the levels did not drop to normal. β2M levels remained persistently high despite completing TB treatment. Interpretation & conclusions: The fi ndings of the study suggest that both HIV and TB act synergistically to activate the host immune system. Although ATT was effective in clearing M. tuberculosis infection, a high proportion of HIV+ TB patients continued to have levels well above the normal range, indicating that underlying immune activation persists despite TB treatment. None of the markers were specific enough to be used to assess cure of TB.

Keratinocyte and lymphocyte apoptosis: relation to disease outcome in systemic lupus erythematosus patients with and without cutaneous manifestations

To investigate the relation of keratinocyte and lymphocyte apoptosis and macrophage function to disease activity and severity in SLE patients with and without cutaneous manifestations. Fifty SLE patients [25 with cutaneous manifestations [group I], 25 without cutaneous manifestations [group II]] and 20 normal controls [group III] were studied. SLEDAI score was used to assess lupus activity. Peripheral lymphocyte apoptosis by Annexin V, macrophage function by serum neopterin and immunohistochemical detection of apoptotic cells in the skin by p.53 were done. Renal biopsy was done in indicated cases. Mean SLEDAI score was significantly higher in group I than II [18.6 +/- 6, 8.8 +/- 2.7 respectively, p<0.001]. The mean percentage of peripheral apoptotic lymphocytes was significantly higher in group I compared to group II and III [55.3 +/- 21.4, 25.6 +/- 8. 7 and 19.4 +/- 3.2 respectively, p<0.001] and so was the serum neopterin level [27.5 +/- 7.3, 14.9 +/- 2.7, 9.4 +/- 1.1 respectively, p<0.001]. The mean number of P53+ve keratinocytes of group I was significantly higher than group II and III [20.6 +/- 5.4, 1.6+0.5, 1.7 +/- 0.4 respectively, p<0.001]. A higher percentage of class IV and V glomerulonephritis was found in group I [47%, 26%, respectively] compared to group II [11% both] [p<0.001]. The mean number of p53+ve keratinocyte showed a significant positive correlation to SLEDAI score, percentage of peripheral apoptotic lymphocytes and serum neopterin [p<0.001]. Accumulation of apoptotic keratinocytes and lymphocytes in SLE seems to be crucial in the pathogenesis of skin lesions and in triggering systemic disease activity and organ damage

Plasma neopterin and peroxide levels in pulmonary tuberculosis patients on chemotherapy with or without micronutrient supplementation

Neopterin and H2O2 are products of cellular [macrophage] activation. The exact roles of these secretions by activated macrophages in protection against tuberculosis remain unclear. In the present study, the changes in the levels of neopterin and total plasma peroxides [TPP] were assessed in pulmonary tuberculosis [PTB] patients on chemotherapy with [C+M] or without [C- M] micronutrient supplementation. Thirty-eight newly diagnosed PTB patients were selected for this study. Twenty patients were treated with anti-tuberculosis drugs and micronutrient [C+M] while 18 PTB-patients were treated with only anti-tuberculosis chemotherapy [C-M]. Plasma neopterin and TPP concentrations were measured by enzymes linked immunosorbent assay [ELISA] and colorimetric method respectively. All PTB patients had elevated neopterin [p=0.02] and TPP [p=0.00] levels when compared with the non-PTB controls. Plasma level of neopterin and TPP declined significantly in C+M after 2 weeks of treatment [p= 0.00, p=0.01 respectively] and also after 4 weeks of treatment [p = 0.01 and p=0.00 respectively] when compared with baseline levels before treatment. No significant change was observed in the levels of neopterin and TPP in C-M after 4 weeks of treatment when compared with baseline value before treatment. Micronutrient supplementation enhanced the decline in the levels of neopterin and TPP after two weeks of treatment. Chemotherapy alone did not produce significant reduction. Therefore, micronutrient supplementation of PTB drugs with synthetic antioxidants or naturally occurring ones [fruits and vegetables] should be attempted

Serum neopterin and zinc levels as biological markers of the HCV disease progression

In chronic hepatitis C virus [HCV] infection, both oxidative stress and the effectiveness of the host immune response contribute to its progression to cirrhosis and the development of hepatocellular carcinoma [HCC]. Neopterin is produced by monocyte-derived macrophages after stimulation with interferon-gamma [IFN- gamma] released from activated T- lymphcytes or other immune activators. High neopterin production is associated with increased production of reactive oxygen species [ROS]. Zinc plays an important role in cell-mediated immune function and it has also anti inflammatory and antioxidant properties which can neutralize free radicals and may protect liver cells from the potential damage they cause. To investigate the relationship between serum levels of neopterin and immune-regulated micronutrients [Zn] with chronic HCV infection progression mediated by increased cellular oxidative stress [malondialdehyde, MDA]. The study included 60 subjects that were divided into two groups: Group I comprised 40 chronic HCV patients further subdivided according to liver biopsy inflammatory grading into: 18 patients with mild active hepatitis [Ia], 16 patients with moderate active hepatitis [Ib] and 6 patients with liver cirrhosis [Ic]. Group II comprised 20 healthy volunteers as control. Serum Zinc was measured by atomic absorption spectrophotometer [AAS], neopterin by ELISA and MDA by colorimetric method. Serum levels of neopterin and MDA were detected significantly higher in HCV patients than controls. A significant positive correlation was detected between the levels of both markers with the levels of total bilirubin, AST, ALT in HCV patients. Serum levels of neopterin and MDA were significantly elevated in group Ib and Ic HCV patients compared with group la patients, significant low serum level of zinc were detected in HCV patients than controls and were significantly lower in group Ib and Ic HCV patients than group Ia patients. Serum zinc, neopterin and MDA levels may be valuable biomarkers for the assessment of severity of viral hepatic damage in HCV infection

Correlation between old and new immuno-inflammatory markers and disease activity in systemic lupus erythematosus

To compare new SLE activity inflammatory markers with traditional ones. In addition, to correlate those with disease activity index of SLE. Forty-three patients fulfilling the American College of Rheumatology criteria for diagnosis of SLE and 20 apparently healthy controls were subjects for study. Neopterin, soluble intercellular adhesion molecule [sICAM-1] and soluble vascular cell adhesion molecule [sVCAM-1] were measured as well as anti-dsDNA antibodies, C3, C4 and CRP. The British Isles Lupus Assessment Group [BILAG] disease activity index was used to measure disease activity. Twenty-four [55.8%] patients had active SLE [total BILAG score > 5], involving more than one system in nine [37.5%]. Activity was more in musculoskeletal, mucocutaneous, and hematological systems. All markers showed significant differences between SLE patients and controls. Neopterin, sVCAM and CRP were highest when compared to controls [p>0.001] as well as to inactive subgroup. The level of sICAM-1 in active was insignificantly higher than inactive group. Significant correlations were found between total BILAG score and CRP, neopterin, sVCAM. No positive correlation was found between any marker and disease activity of different BILAG organ systems. All tests were done for 22 patients on 3 occasions over 6 months. Highest levels of sVCAM-1 were in active subgroup with flares during the first measurement. Significant decrease between first and third measurement was observed within all subgroups. Neopterin and sVCAM-1 appear to be clinically useful for isolated and serial concentrations assessments of SLE disease activity scored using the BIIAG index. Anti-dsDNA and sVCAM-1 are good markers to predict remission

Serum neopterin as a marker of severity of unstable angina

The current study aimed to assess serum neopterin level in patients with chronic stable angina and unstable angina and to assess the relation between neopterin concentration and complex coronary artery stenosis in patients with unstable angina. There is increasing evidence that inflammation plays an important role in atherogenesis and may determine plaque vulnerability. At angiography, disrupted or ulcerated plaques appear as complex stenosis. Plaque vulnerability has been shown to be a function of the increased local number of inflammatory cells within plaques, particularly activated macrophages and lymphocytes. Neopterin is a pterydine derivative produced by activated macrophages, so it can be used as a marker for severity in patients with unstable angina. Fourty patients were involved in this study [30 patients with the diagnosis of unstable angina and 10 patients with the diagnosis of chronic stable angina], ten healthy subjects of matched age and sex were involved as control group. All members of the study were subjected to complete medical history, general and local cardiac examination, 12 lead ECG, echocardiography, and the following laboratory investigations: CK and CKMB, C-reactive protien, Neopterin level, serum cholesterol, LDL, HDL, triglycerides, creatinine, urea and blood glucose. Coronary angiography was done to all members of group 1 [patients with the diagnosis of unstable angina]. Our study revealed that: Neopterin level was significantly higher in patients with ischaemic heart disease than in healthy controls. It was also significantly higher in patients with unstable angina than in patients with chronic stable angina. Neopterin and CRP levels were significantly correlated with the presence of multiple complex lesions in angiography. There is a strong association between neopterin level and the number of complex lesions in angiography in patients with unstable angina, so, it can be used in risk stratification in these patients