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Showing papers on "Neopterin published in 1994"


Journal ArticleDOI
TL;DR: The hypothesis that major depression is accompanied by an immune response and that the lower L-TRP availability in that illness may be an epiphenomenon of immune activation is supported.
Abstract: There is now some evidence that major depression may be accompanied by an immune response. The latter condition is suggested by elevated secretion of neopterin and interferon-γ (IFNγ) and by lower L -tryptophan ( L -TRP) plasma levels. This study investigated the plasma levels of neopterin, L -TRP, and the L -TRP/competing amino acids (CAA) ratio in 30 normal control subjects and 47 depressed subjects (16 minor depressed, 13 simple major depressed, and 18 melancholic subjects), and IFNγ secretion by mitogen-stimulated peripheral blood mononuclear cells in 7 normal control subjects and 13 major depressed subjects. Plasma neopterin levels were significantly higher in depressed subjects than in normal controls; 61% of melancholic patients had increased neopterin levels (⩾ 7 nmol/1) with a specificity of 90%. Patients with major depression had significantly lower L -TRP and L -TRP/CAA values compared with normal control subjects. The amino acid values were significantly and negatively correlated with plasma neopterin levels. Major depressed subjects exhibited significantly higher IFNγ secretion than did normal control subjects. The results further support the hypothesis that major depression is accompanied by an immune response and that the lower L -TRP availability in that illness may be an epiphenomenon of immune activation.

275 citations


Journal ArticleDOI
TL;DR: It is demonstrated that prostaglandins are increased in the central nervous system in HIV‐associated dementia and may play a role in the development of neurological dysfunction.
Abstract: The dementia associated with human immunodeficiency virus (HIV) is poorly understood. Dementia is accompanied by infection and activation of macrophage lineage cells in the brain and production of toxic products by these cells has been postulated to play a role in the pathogenesis of dementia. Eicosanoids are potential products of activated macrophages that can mediate cell injury. We measured the levels of prostaglandin E2 in the cerebrospinal fluid of HIV-positive individuals with dementia and/or myelopathy and compared these levels with those of HIV-negative patients with other neurological diseases and HIV-positive patients without dementia. Cerebrospinal fluid prostaglandin E2 levels were increased in dementia. This increase was associated with severity of dementia and correlated with cerebrospinal fluid levels of neopterin and beta 2-microglobulin. Prostaglandins F2 alpha and thromboxane B2, additional products of the cyclooxygenase pathway of arachidonic acid metabolism, were also elevated in dementia, but leukotriene C4, a product of the lipoxygenase pathway was not. Since synthesis of prostaglandins is regulated in part by the levels of inducible forms of cyclooxygenase, we measured the levels of cyclooxygenase-1 and 2 mRNAs in the brains of HIV-positive individuals with and without dementia by reverse transcriptase polymerase chain reaction. Levels of intact cyclooxygenase-1 mRNA were higher in the brains of demented individuals, but this did not reach statistical significance. These data demonstrate that prostaglandins are increased in the central nervous system in HIV-associated dementia and may play a role in the development of neurological dysfunction.

231 citations


Journal ArticleDOI
TL;DR: Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values, and there were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations.

205 citations


Journal ArticleDOI
TL;DR: HIV-infected patients with abnormally low 1,25D levels had shorter survival times and did not appear to be related to vitamin D deficiency, as well as serum levels of CD4+ cell counts in peripheral blood.
Abstract: Vitamin D metabolites, immunologic, virologic, and clinical parameters, and survival time were determined in 22 asymptomatic human immunodeficiency virus (HIV)-infected patients (CDC stage II/III), 31 symptomatic HIV-infected patients (CDC stage IV), and 28 HIV-seronegative controls. Significantly lower serum levels of 1,25-vitamin D (1,25D) were found in symptomatic patients (median, 34 pg/mL; 25th-75th percentile, 21-45) compared with controls (49 pg/mL; 39-59) and asymptomatic patients (45 pg/mL; 42-50). In HIV-infected subjects, the serum level of 1,25D was positively correlated with CD4+ cell counts in peripheral blood (r = .35, P < .05) and negatively correlated with the level of serum neopterin (r = -.36, P < .01). HIV-infected patients with abnormally low 1,25D (< 25 pg/mL) also had shorter survival times than other HIV-infected subjects (P < .01). Low 1,25D levels did not appear to be related to vitamin D deficiency.

141 citations


Journal ArticleDOI
TL;DR: The data show that the macrophage-derived immune activation marker neopterin is closely correlated with the extent of carotid atherosclerosis, and chronic activation of immune cells, preferentially of macrophages, may play a key role in atherogenesis and/or progression of Atherosclerosis.

129 citations


Journal ArticleDOI
TL;DR: In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha,IL-4, and sIL-2R correlated significantly with one another and with relative amounts of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells.
Abstract: Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.

126 citations


Journal Article
TL;DR: The authors investigated 63 individuals with HIV infection, 34 of whom were asymptomatic (nine had oral candidiasis, four had constitutional signs and symptoms, and 16 had AIDS), for plasma lipids, soluble tumor necrosis factor receptor 75 (sTNF-R75) and other immune activation markers, namely urinary neopterin, beta 2-microglobulin, and the CD4+ T cell count.
Abstract: We investigated 63 individuals with HIV infection, 34 of whom were asymptomatic (nine had oral candidiasis, four had constitutional signs and symptoms, and 16 had AIDS), for plasma lipids, soluble tumor necrosis factor receptor 75 (sTNF-R75) and other immune activation markers, namely urinary neopterin, beta 2-microglobulin, and the CD4+ T cell count. The median CD4+ T cell count was 318 x 10(6)/L. All individuals were allowed to have light breakfast in the morning; the venipuncture for the plasma lipids was done between 11 a.m. and 3 p.m.. Decreased plasma concentrations were found for total cholesterol, and HDL and LDL cholesterol in 3.2%, 46%, and 56% of the subjects, respectively. Plasma triglyceride levels were increased in 31.7% of the study population. The frequency and the extent of the decrease of HDL and LDL cholesterol and the increase in triglyceride levels were greater in those with a CD4+ T cell count below the median (p = 0.003, p = 0.05, and p = 0.01); when comparing individuals with CD4+ T cell counts above and below 500 x 10(6)/L (19 individuals), a difference was only found for HDL cholesterol (p = 0.01). Plasma levels of triglycerides correlated significantly however weakly with serum concentrations of sTNF-R75 (rs = 0.32, p = 0.01) but not at all with urinary neopterin or serum beta 2-microglobulin. HDL cholesterol correlated inversely with sTNF-R75 (rs = -0.53, p < 0.0001) and to a lesser extent with urinary neopterin (rs = -0.46, p = 0.0003) and beta 2-microglobulin (rs = -0.34, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

94 citations


Journal ArticleDOI
01 Oct 1994-AIDS
TL;DR: The relationship between high proviral DNA level in PBMC, high viral load in plasma, elevated β2M and neopterin concentrations in serum, and the presence of p24 antigen in serum is demonstrated, suggesting the possible usefulness of proviral load as an early indicator of disease progression.
Abstract: OBJECTIVE We compared the proviral DNA level in peripheral blood mononuclear cells (PBMC), viral RNA level in plasma, presence of p24 antigen in serum, viral phenotype, and results of immunological markers of HIV-1 disease. METHODS Consecutive samples of 62 HIV-1-infected patients, representing all stages of disease were tested for proviral DNA in PBMC and viral RNA in plasma using a semi-quantitative limiting dilution polymerase chain reaction (PCR). The presence of a syncytium-inducing (SI) phenotype was assessed after direct cocultivation of patient PBMC with MT-2 cells. Results of the quantitative PCR and the MT-2 coculture were correlated with the clinical stage of the disease, with the number of CD4+ T cells, and with the results of other virological and immunological markers, such as the level of p24 antigen, beta 2-microglobulin (beta 2M) and neopterin. RESULTS Significant differences were observed between the results for asymptomatic and symptomatic patients for all markers under study. In the group of asymptomatic patients with a CD4+ T-cell count > 200 x 10(6)/l, patients with high amounts of proviral DNA had significantly higher amounts of beta 2M, neopterin and viral RNA, they were more frequently p24 antigen-positive and harboured more frequently SI strains than patients with low amounts of proviral DNA. A good correlation between the proviral DNA and the viral RNA levels was observed. Significant changes of viral RNA but not proviral DNA levels were observed after initiation of therapy or when therapy failed. CONCLUSIONS We demonstrated the relationship between high proviral DNA level in PBMC, high viral load in plasma, elevated beta 2M and neopterin concentrations in serum, and the presence of p24 antigen in serum in a group of asymptomatic patients with a CD4+ T-cell count > 200 x 10(6)/l. We suggest the possible usefulness of proviral load as an early indicator of disease progression. The presence of SI strains is highly correlated with disease; however, SI strains were detected in only 46% of symptomatic patients. It also appeared that the measurement of viral RNA levels is a useful marker for therapy monitoring.

82 citations


Journal ArticleDOI
TL;DR: It is demonstrated that neopterin enhances hydrogen peroxide effects only in the presence of iron chelator complexes like iron‐(III)‐ orIron‐(II)‐EDTA or iron-(III)'sDTPA, which may play an important role in macrophage‐mediated effector mechanisms.

77 citations


Journal ArticleDOI
TL;DR: Findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or β2m levels, which were higher among white than blacks and higher among users of antihistamines.
Abstract: Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2-microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels.

68 citations


Journal Article
TL;DR: The findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.
Abstract: Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.

Journal ArticleDOI
TL;DR: In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis, probably reflecting a characteristic immunological dysregulation in these patients.

Journal Article
TL;DR: By comparing urine and serum neopterin concentrations in HIV seropositive and seronegative human individuals, a strong correlation and similar diagnostic sensitivity between urinary and serum values was observed, and neopterIn concentrations in serum or urine seem of equal value for diagnostic application as long as renal function is normal.

Journal ArticleDOI
TL;DR: It is concluded that cytokine release associated with evolving septic shock in patients with AML does not depend on circulating leucocytes.
Abstract: Septic shock is the major cause of treatment-related death in patients with acute myelogenous leukaemia (AML) undergoing intensive chemotherapy. Interleukins (IL)-1 beta, -6, -8, and tumour necrosis factor alpha (TNF-alpha) have been implicated as mediators of septic shock, with circulating leucocytes being considered a major source for their release. However, plasma cytokine levels of leucocytopenic patients with evolving sepsis have not been studied. We have prospectively measured plasma cytokines during chemotherapy-induced leucocytopenia (< 1 x 10(9)/l) in 50 patients with AML. Cytokine levels in patients with severe sepsis (n = 5) or septic shock (n = 8) were compared to those measured in 13 matched patients with uncomplicated febrile infections. In evolving septic shock, IL-6, IL-8 and TNF-alpha peaked within 48 h of fever onset at levels reported for non-leucocytopenic patients and distinctively higher than during uncomplicated febrile episodes (P < 0.05). Peak concentrations measured within 48 h after onset of fever were related to fatal outcome. IL-1 beta was detected in less than 5% of all samples. Cytokine concentrations were unrelated to leucocyte counts and markers of neutrophil or monocyte activation (elastase and neopterin levels, respectively). We conclude that cytokine release associated with evolving septic shock in patients with AML does not depend on circulating leucocytes.

Journal ArticleDOI
TL;DR: The aim of this study was to investigate whether an association in HIV infection exists between the serum levels of TNF alpha, the two soluble TNF receptors (sTNFRs) and other soluble immune activation markers, namely neopterin and beta 2-microglobulin, and the number of CD4+ T-cells.

Journal ArticleDOI
TL;DR: It is suggested that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.
Abstract: Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.

Journal ArticleDOI
TL;DR: In certain situations all three substances, namely neopterin, 7,8‐dihydroneopterin and cGMP, may be present locally and even in the circulation at the same time and would significantly enhance the risk of c‐fos gene expression and therefore promote tumour growth and development.

Journal ArticleDOI
TL;DR: HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-γ, irrespective of therapy outcome.
Abstract: To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1β, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P=0.0026), β2-microglobulin (P=0.046), soluble interleukin-2 receptor (P=0.021), and soluble CD8 (P<0.039), than healthy controls; conversely, interferon-γ levels were significantly lower (P=0.023). Significant correlations were observed between β2-microglobulin concentration and Knodell's index (r=0.638,P=0.00045), the score of piecemeal necrosis (r=0.572,P=0.0023), and the degree of fibrosis (r=0.527,P=0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r=0.412,P=0.037), and the degree of lobular cytolysis (r=0.389,P=0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P=0.042) in patients with a sustained biochemical response. On interferon-α treatment, the levels of β2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P<0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-γ.

Journal ArticleDOI
TL;DR: Measurement of the sHLA-I antigen level may provide useful prognostic information in HIV-positive subjects and its predictive value in combination with serum beta 2-mu level, neopterin level, or CD4+ T-cell percentage is greater than that of each individual variable.

Journal ArticleDOI
TL;DR: The data show that rhlL-12 has multiple effects on peripheral hematology and suggests that this model may be useful to investigate in vivo bioactivity of rhl L-12, and shows that thrombocytopenia and anemia were noted in both treated groups as compared to controls.

Journal ArticleDOI
TL;DR: The relationship between NO biosynthesis and changes in immunological and vascular parameters during IL‐2 therapy in 13 patients with metastatic cancer is described.
Abstract: Hypotension is a dose-limiting side effect of interleukin-2 (IL-2) therapy. This may be due to increased biosynthesis of the potent vasodilator nitric oxide (NO) induced by cytokines such as tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which are known to be generated during IL-2 therapy. We describe the relationship between NO biosynthesis and changes in immunological and vascular parameters during IL-2 therapy in 13 patients with metastatic cancer. Plasma concentrations of neopterin and nitrite plus nitrate (NOx) were higher in cancer patients prior to treatment compared with normal subjects (neopterin; 10·8±1·4 vs. 2·0±0·4 ng ml-1, P<0·001: NOx; 45±6 vs. 28±2 μM, P<0·005). Pretreatment TNF-α and IFN-γ plasma concentrations were not significantly different in cancer patients from those in controls. During infusion of IL-2 (18 times 106 international units m-2 per day for 5 days) these parameters increased, reaching maximal concentrations at day 3 for IFN-γ and day 5 for TNF-α, neopterin and NOx. The maximal induced NOx correlated with maximal TNF-α (r = 0·60, P<0·04), IFN-γ (r = 0·63, P<0·02) and neopterin (r = 0·66, P<0·01). As plasma NOx concentrations increased, systolic blood pressure fell, reaching a minimum at day 3 despite a continued rise in NOx concentrations. These changes were accompanied by a continuous increase in pulse rate throughout the infusion period. These findings indicate that induction of NO biosynthesis contributes to hypotension induced during IL-2 therapy. Inhibitors of NO synthase may be useful in limiting toxicity, thus allowing administration of higher and possibly more efficacious doses of this cytokine in the treatment of cancer.


Journal Article
TL;DR: Findings in a limited number of patients suggest that calprotectin levels may reflect immune activation and other immune mechanisms correlated with enhanced antimicrobial defense induced at least transiently by antiviral treatment.
Abstract: The calcium-binding myelomonocytic protein calprotectin (L1 protein) was quantified in serum from 51 patients with HIV infection and in 20 HIV-seronegative blood donors. Significantly elevated levels were found both in asymptomatic patients and in people with AIDS compared with controls. The calprotectin level was not related to ongoing or recent opportunistic infections. For patients with CD4+ counts above 50 x 1 million/L a significant negative correlation was found between serum calprotectin levels and the CD4+ counts. Serial samples from 24 patients during their first year of zidovudine (ZDV) treatment showed a further elevation of serum calprotectin during the first months of ZDV treatment with a subsequent decline to pretreatment levels. A low calprotectin response during the first 6 months determined as area under the curve was associated with the occurrence of at least one AIDS-defining infection during the first year of antiviral treatment. Also a low calprotectin maximal response during ZDV therapy was associated with short survival. Similar associations were not found for neopterin beta2-microglobulin HIV p24 antigen or CD4+ or CD8+ lymphocytes in blood. The authors findings in a limited number of patients suggest that calprotectin levels may reflect immune activation and other immune mechanisms correlated with enhanced antimicrobial defense induced at least transiently by antiviral treatment. (authors)

Journal ArticleDOI
TL;DR: Initial evidence is provided that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE.
Abstract: OBJECTIVE--To investigate the role of serial measurement of urine neopterin concentration in monitoring the progression of systemic lupus erythematosus (SLE) disease activity scored using the British Isles Lupus Assessment Group (BILAG) index. METHODS--We followed prospectively 68 unselected SLE patients for a total of 464 patient months during which 233 separate assessments were carried out. At each assessment, urine neopterin, determined by high performance liquid chromatography, together with erythrocyte sedimentation rate (ESR) and plasma C3, C4, and C3d were measured and the SLE disease activity scored by a single observer. Serial data sets were analysed using time series modelling techniques. RESULTS--Single time point analysis showed a significant increase in urine neopterin concentrations in 14 patients who suffered flares of their disease during the study period (p = 0.02). Thirty patients with active disease went into disease remission with significant decreases in their urine neopterin values (p = 0.02). In the time series analysis, a statistically significant association was found between serial concentrations of urine neopterin and BILAG score (r = 0.6, p < 0.05); no other study parameter (ESR and serum C3, C4, and C3d) mirrored SLE disease activity as effectively. CONCLUSIONS--This study provides initial evidence that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE. Consequently, serial urine neopterin measurements appear to be clinically useful for monitoring disease activity and may contribute substantially to therapeutic decision making in these patients.

Journal Article
TL;DR: Cellular viremia, like CD4+ T cell count, reflects the patient's status at the time of assessment, and could be more informative for the prediction of future clinical progression than p24 antigenemia, which was correlated with only biological markers of immune activation as beta 2-microglobulin and neopterin levels.
Abstract: Surrogate markers generally used for observation of patients infected with human immunodeficiency virus (HIV) and their plasma and cellular viral load were assayed in a series of 40 patients before initiation of zidovudine therapy. Plasma viremia was positive in 62.5% of patients and was statistically correlated with clinical stage, CD4+ T cell count, CD8+ T cell count, beta 2-microglobulin level, neopterin level, and immunoglobulin A level. Cellular viremia was positive in 95% of patients and was correlated with clinical stage, CD4+ T cell count, beta 2-microglobulin, neopterin levels, and disease progression during the following months. A discordance was found between p24 antigenemia, even after acid dissociation of immune complexes, and plasma viremia. In fact, p24 antigenemia was correlated with only biological markers of immune activation as beta 2-microglobulin and neopterin levels. The measurement of anti-p24 antibodies did not appear discriminative in our staging. Plasma viremia, like CD4+ T cell count, reflects the patient's status at the time of assessment. Cellular viremia could be more informative for the prediction of future clinical progression.

Journal ArticleDOI
TL;DR: To measure markers of inflammation in a cohort of young and old subjects and relate these findings to the functional level of the individuals, a large number of the subjects had previously had a history of inflammation.
Abstract: OBJECTIVE: To measure markers of inflammation in a cohort of young and old subjects and relate these findings to the functional level of the individuals. DESIGN: For the pilot study, blood samples were obtained from 18 young (age 20–35 years) and 18 old (age 68–83 years) subjects. The main study population included community-dwelling subjects between the ages of 70 and 79. The group consisted of 282 subjects with minimal physical limitations, 17 subjects from the middle third, and 16 from the lower third of physical function rankings. METHODS: Plasma markers were measured by ELISA techniques, and certain biochemical values were obtained through routine clinical tests performed by a commercial laboratory. RESULTS: D-Dimers were higher for physically impaired subjects in all groups, but most prominently among black females, who also had significantly higher D-Dimer levels in every functional group. To inquire whether higher D-Dimers were associated with markers of inflammation, we also examined the macrophage metabolite, neopterin, the neutrophil product, elastase complexed to antitrypsin (E/a), and the albumin globulin ratio (A/G ratio). No differences were found in neopterin or E/a levels on the basis of gender, race, or functional status. The A/G ratio was significantly lower in functionally impaired subjects. CONCLUSION: These preliminary findings demonstrate racial/ethnic and gender differences in D-Dimers in a population of community-dwelling elderly, and suggest that factors influencing hemostasis may be particularly relevant to physical functional status in black women. A sample containing more subjects with lower physical function will be needed to establish the relationship between inflammation, altered hemostasis, and physical function decline.

Journal ArticleDOI
TL;DR: The red cell distribution width, the morphological results, the enhanced macrophage activation state, as well as the results of the iron status, point towards a contribution of an immune-associated functional iron deficiency to the anemia of SICU patients.
Abstract: BACKGROUND: The cause of the anemia of patients in surgical intensive care units (SICU) is not completely clear but is likely to be multifactorial. This study investigated a possible role for immune activation in the anemia of SICU patients. METHODS: Neopterin plasma levels, as a measure of T-cell-macrophage-axis activation, RBC-counts, Hb, Hct, MCV, MCH, MCHC, RDW, HDW, red cell morphology and iron status were determined in a group of 47 SICU patients. RESULTS: The study confirms the presence of a moderate anemia (Hb = 10.38 +/- 13 g/dL) in SICU patients. Abnormal red blood cell morphology was observed in 82% of all patients over at least part of their ICU-stay. Markedly enhanced T-cell-macrophage-axis activity was evidenced by a significant increase in the plasma neopterin levels of the patient group (44 +/- 79.6 nmol/L) compared to that of the control group (3.38 +/- 4.9 nmol/L). Iron metabolism was found to be disturbed. CONCLUSIONS: The red cell distribution width, the morphological results, the enhanced macrophage activation state, as well as the results of the iron status, point towards a contribution of an immune-associated functional iron deficiency to the anemia of SICU patients.

Journal ArticleDOI
TL;DR: A role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis is indicated.
Abstract: Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.

Journal ArticleDOI
TL;DR: Elevated serum and CSF s-ICAM-1 levels already in asymptomatic HIV-1-positive individuals add to the evidence for an early immune activation in HIV infection, and could serve as a new surrogate marker similar to neopterin.

Journal ArticleDOI
TL;DR: Evaluated soluble interleukin-2 receptors, neopterin and adenosine deaminase in pleural effusions from 93 patients with tuberculosis, malignancies, uremia, pneumonia and other kinds of pleurisy found them to be related to TB in origin.
Abstract: We evaluated soluble interleukin-2 receptors (sIL-2R), neopterin and adenosine deaminase (ADA) in pleural effusions from 93 patients with tuberculosis, malignancies, uremia, pneumonia and other kinds of pleurisy There were significantly elevated ADA (1027 +/- 47 U/l) and sIL-2R (8,238 +/- 4,117 U/ml) values in tuberculous (TB) pleural fluids as compared with other non-TB pleural fluids (p < 0005) The neopterin levels in pleural fluid were significantly lower in the cancer group (173 +/- 78 nmol/l; p < 0005) and most strikingly elevated (3094 +/- 1122 nmol/l; p < 00001) in patients with uremic pleural effusions Using cut-off values of 60 U/l in ADA and 5,000 U/l in sIL-2R, 920 and 869% of pleural effusions were TB in origin Eighty-four percent of patients with malignant pleural effusions had neopterin levels less than 25 nmol/l