Showing papers on "Neopterin published in 1991"

Neopterin and interferon‐gamma in serum and cerebrospinal fluid of patients with HIV‐associated neurologic disease

Abstract: We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.

Biological and Clinical Effects of Intravenous Tumor Necrosis Factor-α Administered Three Times Weekly

Abstract: Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological and antitumor effects in vitro and in mouse models. The immunological effects of the molecule as a single agent, however, have not been well studied clinically. We conducted a Phase I trial of TNF in 53 patients with advanced malignancies in order to determine the biological and clinical effects of TNF when administered as a 30-min i.v. infusion three times/week. Dose levels of TNF ranged from 5 to 275 micrograms/m2; doses of TNF were escalated between patient groups. The most common clinical toxicities of TNF consisted of rigors, anorexia, headache, and fatigue. Dose-limiting toxicity consisted of hypotension, fatigue, and nausea. Four patients treated at the maximally tolerated dose of 225 micrograms/m2 received dexamethasone to determine whether the toxicities of TNF could be ameliorated. No significant differences in hypotension or subjective symptomatology were observed in those patients receiving dexamethasone and those who did not or between injections in which dexamethasone was administered and when it was not. One patient with colorectal carcinoma treated with 50 micrograms/m2 had a partial response lasting about 9 months. Biological responses were evaluated in 8 patients treated at the maximally tolerated dose before therapy and 24 h afterward. TNF significantly (P less than 0.05 for all) enhanced serum beta 2-microglobulin, serum neopterin, and serum interleukin-2 receptor (Tac antigen) levels. Indoleamine 2,3-dioxygenase activity was also increased 24 h following the administration of TNF, although this increase was only of borderline statistical significance (P = 0.07). TNF did not enhance granulocyte bactericidal activity. The expression of cell surface proteins on monocytes, including HLA-DR, HLA-DQ, beta 2-microglobulin, and the Fc receptor, and serum interleukin-1 activity also were not significantly increased by the administration of TNF. Thus, in humans TNF caused biological response modulation with evidence of HLA Class I (beta 2-microglobulin) increase and T-cell (Tac antigen) and monocyte (neopterin) activation.

Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters.

Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine involved in the regulation of the terminal differentiation pathway of B lymphocytes. Recent reports revealed its potential role in the in vitro and in vivo growth of human multiple myeloma cells. The mechanism, however, by which IL-6 triggers proliferation of malignant plasma cells remains controversial. Using the very sensitive 7TD1 bioassay we quantified endogenous circulating IL-6 levels in serum samples of 104 patients suffering from monoclonal gammopathies and other hematological disorders [47 with multiple myeloma (MM), 24 with monoclonal gammopathy of unknown significance (MGUS), 8 with myeloproliferative disease, and 25 suffering from lowgrade non-Hodgkin's lymphoma (NHL)]. Elevated serum levels of IL-6 (>5 pg/ml) were detected in 42% of the patients with MM, in 13% with MGUS, in 15% with low-grade B-NHL, and in 1 patient with T-NHL. In patients suffering from chronic myeloproliferative diseases, IL-6 levels were within the normal range. In patients with myeloma, IL-6 levels were significantly higher at advanced stages (II/III) or with progressive disease than in patients with MM stage I, MGUS, or at the plateau phase (P<0.01). In patients with monoclonal gammopathies including MGUS, serum IL-6 levels correlated with neopterin, tumor necrosis factor alpha and β2-microglobulin. An inverse correlation was found with hemoglobin levels. From these results, we propose that in myeloma patients serum IL-6 levels may reflect disease activity and tumor cell mass. The correlation with serum neopterin, a macrophage product, also suggests its origin in an activated immune system.

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

Abstract: OBJECTIVE--To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN--Retrospective study of changes in laboratory markers and survival. SETTING--Multicentre trial at university hospital clinics. SUBJECTS--90 Patients with AIDS or AIDS related complex. INTERVENTION--Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES--Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS--The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION--These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

The initial immune response to HIV and immune system activation determine the outcome of HIV disease.

Abstract: A study was conducted to assess the relative contribution of the HIV-1-specific immune response and -nonspecific immune activation to HIV disease progression. The titer of antibody to the p24 core protein and the concentration of serum neopterin were measured in 238 HIV-1-seropositive subjects in a prospective cohort study of homosexual men. Antibody titers were extremely variable among cohort participants but relatively stable over time, suggesting inherent differences in the initial immune response capacity. Neopterin concentrations were also variable at cohort entry but generally increased over time. These two markers, measured at cohort entry, had powerful and independent predictive value for the development of AIDS up to 54 months before diagnosis. Subjects with low antibody titers and high levels of neopterin, had the highest incidence of AIDS (60% over 54 months). Patients with low antibody or high neopterin alone had an intermediate risk (34% incidence) and less than 10% of those with high antibody and low neopterin developed AIDS. We propose that the initial immune response to HIV and virus-mediated immune system activation are independent and innately variable components of an individual's response to HIV infection that interact to determine the clinical outcome.

Posttransplant neopterin excretion in renal allograft recipients--a reliable diagnostic aid for acute rejection and a predictive marker of long-term graft survival.

Abstract: During the immediate posttransplant period, daily measurements of urinary neopterin, which is produced by stimulated macrophages, were evaluated in 294 consecutive recipients of renal allografts for their diagnostic value in acute graft rejection. The ability of mean and peak neopterin excretion values to predict long-term graft survival was analyzed on the basis of an eight-year follow-up. Immunosuppressive therapy (cyclosporine +/- prednisone versus azathioprine + prednisone) and initial nonfunction did not influence neopterin excretion. In patients with rejection episodes and in those with infections, neopterin levels were significantly increased. Diagnostic sensitivity and specificity with regard to rejection diagnosis were assessed for different levels of neopterin. By statistical analysis, a significant association between increased neopterin and higher risk of rejection was found, which was particularly pronounced in patients receiving cyclosporine. Increase in neopterin excretion preceded clinical rejection diagnosis by up to four days. Peak neopterin values above 800 mumols/mol urinary creatinine observed during the posttransplant period, were associated with significantly poorer graft survival. A multivariate analysis showed that peak neopterin levels, age of patients, and early posttransplant presence/absence of acute rejection were significant and independent joint predictors for long-term graft survival. Measurement of neopterin can be of help as an additional marker in early diagnosis of renal allograft rejection, and high neopterin values during the initial posttransplant period are associated with poorer long-term graft survival.

Predictive Value of Interleukin-6 and Neopterin in Patients with Multiple Myeloma

Abstract: Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman9s rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models.

Immune activation markers and AIDS prognosis.

Abstract: Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.

Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial infection.

Abstract: Serum C-reactive protein and neopterin concentrations were measured in samples taken at an early stage in different types of infection to see whether the combination of markers could contribute to the diagnosis of infection and help distinguish between bacterial and viral infections, tuberculosis, and infections due to "other" pathogens. Both markers were significantly raised in all categories of infection compared with controls, and there were significant differences between the means of both markers when comparing several of the categories of infection. Only C-reactive protein concentrations in bacteraemic patients, however, were both sensitive and specific at distinguishing the type of infection. The additional use of neopterin estimation played only a minor part in increasing the specificity of diagnosis in tuberculosis and in viral infections. On the basis of this study it was not considered worth the time and expense of performing neopterin assays in addition to C-reactive protein estimations to differentiate viral from bacterial infection.

Levels of cytokines in plasma during Plasmodium falciparum malaria attacks.

Abstract: The variation of levels of tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, gamma interferon, neopterin, and interleukin-2 receptors in plasma were monitored in 16 patients presenting with an acute Plasmodium falciparum malaria attack. Relations among cytokine levels and between cytokine levels and hematological and parasitological data were assessed.

Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS.

Abstract: We investigated whether elevated serum levels of beta 2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+ T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. beta 2-Microglobulin and neopterin levels were strongly correlated (r = 0.82), and were each significantly higher in patients with detectable serum interferon-alpha activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+ T-cell count of tumor regression after treatment with interferon-alpha and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-alpha activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, beta 2-microglobulin and neopterin. The level of beta 2-microglobulin was the single best predictor of survival. When beta 2-microglobulin was not considered, the endogenous interferon-alpha variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologic markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+ T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS.

Neopterin in cerebrospinal fluid: a useful marker for diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis.

Abstract: Neopterin is a pyrazino-pyrimidine compound that is biosynthesized from guanosine triphosphate.’ Neopterin may be an in vitro indicator of activation of the immune system. Raised excretion of neopterin is related to the action of interferons on the T lymphocyte/macrophage axis.* Increased urinary neopterin levels occur in patients with malignancies and viral infections, as well as in patients with the acquired immunodeficiency syndrome (AIDS) and generalized lymphadenopathy.3-5 We have measured the levels of neopterin in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized clinically by a symmetric upper motoneuron disorder with urinary sphincter involvement and mild sensory disturbances, and serologically by the presence of antibodies against HTLV-I in serum and CSF.6 Methods. Twenty patients with HAM/TSP, 17 asymptomatic HTLV-I carriers, 6 patients with viral encephalitis, 30 patients with other neurologic disorders, including 6 cases of chronic MS, and 26 normal controls were analyzed. The assay for neopterin involved a pretreatment modified from that of Fukushima and N i ~ o n . ~ CSF and urinary neopterin levels were measured by high-pressure liquid chromatography (HPLC) with fluorometric detection. Each CSF sample (100 pl) was thawed and immediately acidified with 100 pl of ice-cold 0.1 N HCI and kept in ice. Then, 50 1 1 of a 1% 12/2% KI in 0.1 N HCl was added and allowed to react a t room temperature in the dark. After standing for 60 minutes, the mixture was neutralized with 50 1 1 of 1.5% ascorbic acid. The solution was centrifuged at high speed for 1 minute in a Beckmann microcentrifuge. For HPLC, a 100-p1 sample of the supernatant was injected over a C18 column (250 X 4.6 mm) with 7% methanol in water as the mobile phase. The neopterin assay was standardized with similarly treated authentic standards. Results. CSF neopterin values in controls (18.0 ? 5.3 pmol/ml, mean k SD) were in agreement with others. Extremely high values of CSF neopterin were found in patients with HAM/TSP (107.7 f 98.1; p < 0.001, Fisher’s exact test). Patients with viral encephalitides also showed high levels of neopterin in CSF. Other noninflammatory neurologic disorders such as MS, ALS, Parkinson’s disease, or cervical spondylosis showed CSF neopterin levels similar to those of the controls, with values below 30 pmol/ml (figure). Some cases of HAM show mild CSFpleocytosis. However, there was no significant correlation between cell counts and levels of neopterin in CSF. Urine samples were measured after being diluted 100 times. Urinary neopterin levels

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease.

Abstract: To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.

Neopterin and (beta)2-microglobulin as prognostic indices in human immunodeficiency virus type 1 infection

Abstract: The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and β2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and β2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and β2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.

Markers for disease progression in intravenous drug users infected with HIV-1

Abstract: We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.

Urinary neopterin in patients with systemic lupus erythematosus.

Abstract: Concentrations of neopterin were measured in urine specimens from 35 patients with active and eight with inactive systemic lupus erythematosus (SLE). Compared with those of apparently healthy controls, neopterin concentrations were higher in patients with active disease (P less than 0.001) and with inactive disease (P less than 0.01), those in patients with active disease being significantly higher than those in patients with inactive disease (P less than 0.001). The correlation between the neopterin concentration and evidence of disease activity was good. All of the patients with clinically active SLE had increased neopterin, but for only 37.5% (three of eight) did the neopterin concentration exceed the upper normal limit during clinical remission. The increase in neopterin concentration did not correlate with clinical courses or severity of renal function. Moreover, serial determinations of neopterin in active SLE patients showed a rapid decrease of initially high concentration, paralleling a decline of clinical activity after initiation of medical therapy. Thus, urinary neopterin may be a useful marker for monitoring disease activity in SLE patients.

The use of ozone-treated blood in the therapy of Hiv infection and immune disease: a pilot study of safety and efficiacy

Abstract: The use of ozone therapy is reported to be effective in a variety of viral illnesses, including HIV disease. We performed a phase I study of ozone blood treatments in 10 patients in whom no significant toxicity was observed. Three patients with moderate immunodeficiency showed improvement in surrogate markers of HIV-associated immune disease. A phase II controlled and randomized double-blinded study was initiated comparing reinjection of ozone-treated blood, and reinjection of unprocessed blood for 8 weeks, followed by a 4-week observation period. Ozone had no significant effect on hematologic, biochemical or clinical toxicity when compared with placebo. CD4 cell count, interleukin-2, gamma-interferon, beta 2-microglobulin, neopterin and p24 antigen were also unaffected by both treatment arms. In conclusion, ozone therapy does not enhance parameters of immune activation nor does it diminish measureable p24 antigen in HIV-infected individuals.

Plasma neopterin as an adjunct to C-reactive protein in assessment of infection.

Abstract: C-reactive protein (CRP) concentrations are increased in plasma in people with inflammatory conditions and bacterial infections. Plasma neopterin concentrations are increased in people with bacterial septicemias, viral infections, and graft vs host disease. Plasma concentrations of CRP and neopterin were measured daily in 21 bone-marrow transplant (BMT) patients, 64 patients in intensive-care units (ICU), and 12 patients with squamous cell carcinoma of the head and neck (HN). In the BMT patients, plasma neopterin measurements in addition to CRP measurements allowed infectious episodes to be distinguished from graft vs host disease. In the ICU patients, increased concentrations of CRP were not specific for infection and the additional plasma neopterin measurements did not improve this specificity. In all three patient groups, the derivation of a neopterin/CRP ratio was of no clinical use. These three groups of patients showed patterns of CRP and neopterin concentrations characteristic of their underlying diseases, the BMT patients with the immunological activation of graft vs host disease showed predominantly increased concentrations of plasma neopterin, ICU patients with infectious and inflammatory conditions had increased concentrations of both CRP and neopterin in plasma, and the HN group with localized inflammation showed increased plasma concentrations of CRP without increases in neopterin.

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

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

Cerebrospinal fluid and serum neopterin and biopterin in D-retrovirus-infected rhesus macaques (Macaca mulatta): relationship to clinical and viral status.

Abstract: Increases in serum and cerebrospinal fluid (CSF) neopterin concentrations accompany many inflammatory diseases, including infection with HIV-1 and may reflect activation of guanosine triphosphate (GTP) cyclohydrolase 1 by gamma-interferon and other cytokines. In the present study, macaques with clinical simian AIDS (SAIDS) infected with the immunosuppressive type-D retrovirus D/1/California had increased concentrations of CSF neopterin but not of biopterin beginning soon after seroconversion. Normal neopterin concentrations in the CSF were found in macaques with SAIDS-related complex as well as asymptomatic, viremic macaques. CSF biopterin, serum neopterin and serum biopterin concentrations of D/1/California-infected macaques were not different from the levels in control animals. The increase in CSF neopterin may reflect local inflammatory responses and paralleled previously documented changes in L-tryptophan metabolism in these macaques. However, the absence of macrophage infiltrates in the brain of the infected macaques suggests a non-macrophage source of both increased CSF neopterin and tryptophan metabolites in the SAIDS macaques.

Modulation of interleukin-2-induced macrophage activation in cancer patients by the pineal hormone melatonin.

Abstract: The concomitant induction of immunosuppressive events, at least in part mediated by macrophages, would represent one of the mechanisms responsible for the lower activity of IL-2 in vivo than in vitro. Since macrophages have recently appeared to be under neuroendocrine control, the present study was carried out to evaluate the effect of the pineal neurohormone MLT on IL-2-induced macrophage activation during cancer immunotherapy, by determining serum levels of neopterin, which is a specific marker of macrophage activity. The study included 21 advanced cancer patients (lung cancer: 12; renal cancer: 9), 10 of whom received IL-2 subcutaneous therapy alone (1.8 x 10(6) IU/m2 twice daily), or IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Neopterin levels increased in all patients during IL-2 immunotherapy, but neopterin mean peak was significantly higher in patients treated with IL-2 alone than in those who received IL-2 plus MLT. This preliminary study would suggest the possible use of neurohormones to modulate host antitumor immune response during cancer immunotherapy with IL-2.

Neopterin, a marker of cell-mediated immune activation in human pregnancy.

Abstract: High neopterin excretion is closely associated with activation of cell-mediated immunity We studied urine and serum neopterin concentrations and serum interferon-gamma concentrations in normal pregnant women In our study population, neopterin concentrations exceeded the normal range in 663 of 840 samples (79%) Neopterin levels increased with the time of pregnancy Serum samples drawn from women in the third trimester of pregnancy also showed high neopterin concentrations in almost all cases; however, no circulating interferon-gamma was detected Whereas neopterin is able to penetrate into the blood stream because of its small size (M = 253 D), diffusion of interferon-gamma is limited Raised neopterin levels provide evidence for activated cell-mediated immunity during pregnancy