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PubMed2001

Association between homocysteine and neopterin in healthy subjects measured by a simple HPLC-fluorometric method.

OBJECTIVES: Neopterin and homocysteine promote vascular smooth muscle cell proliferation through the activation of nuclear factor(kappa) B. The aim of this study was to investigate the relation between these two compounds in healthy subjects by a rapid HPLC-fluorometric method which simplifies sample pretreatment for the measurement of neopterin in serum. DESIGN AND METHODS: In 40 healthy subjects (45.9 +/- 2.1 yr, mean +/- SEM, 10 males, 30 females) serum neopterin concentrations were measured by HPLC-fluorometry and enzyme-linked immunusorbant assay-ELISA and the results were compared. Urinary neopterin and plasma total homocysteine concentrations were assayed by HPLC-fluorometry. RESULTS: Serum neopterin concentrations measured by HPLC and ELISA were 7.5 +/- 0.4 and 7.4 +/- 0.3 nmol/L, respectively, r = 0.92, p < 0.01. Urinary neopterin level was 163.9 +/- 11.0 nmol/mmol creatinine and plasma total homocysteine 7.6 +/- 0.4 micromol/L. A significant positive correlation was observed between serum neopterin and plasma total homocysteine (r = 0.59, p < 0.01). CONCLUSIONS: A simple and rapid sample pretreatment for the measurement of neopterin in serum has been introduced. The significant positive correlation between neopterin and homocysteine implies that, interference with leukocyte function might be a new possible mechanism for the deleterious effects of homocysteine on vascular function.

Adult↗
PubMed1988

Urinary neopterin in infants with primary immunodeficiency.

Neopterin is produced in large amounts specifically from macrophages upon stimulation with interferon-gamma (IFN-gamma). Measurement of neopterin allows a direct in vivo quantification of T cell activation. This is particularly useful, e.g., in early diagnosis of graft rejection. Since disease states with elevated neopterin levels in some cases are coupled with an impaired cellular immunity, we decided to investigate the possible influence that severely diminished cellular immunity might have on urinary neopterin levels. Our investigation on six children with severe primary immunodeficiency presents some evidence that immunodeficiency itself does not account for an increase in neopterin when patients are free from infections. Neopterin was also normal in an SCID patient who was completely lacking T cells and was suffering from severe infections. Two patients with primary immunodeficiency and residual T lymphocytes suffered from severe infections and showed elevated neopterin. The data support the hypothesis that elevated neopterin levels are dependent on the presence of activated T lymphocytes. Residual T lymphocytes of SCID patients have the capacity to induce neopterin in vivo when patients suffer from infections.

Adenosine Deaminase↗
PubMedDate not supplied

Thermal injury-associated neopterin production: regulation by interleukin-2.

Pteridin neopterin production by monocytes/macrophages has been linked to the biologic activity of immune activation- and/or infection-related cytokines. In patients with thermal injuries who succumb to infections, serum levels of both interleukin-2 (IL-2) and neopterin are significantly increased. However, the relationship between these two markers of immune activation remains unclear. This study examines the role of IL-2 in the biosynthesis of neopterin after major burn. Up to 4 weeks after burn, the levels of plasma neopterin and endotoxin were elevated in all patients studied (N = 9, 30% to > 90% total body surface area). Intact (unsupplemented) peripheral blood mononuclear cell (PBMC) cultures from patients with sepsis secreted high levels of neopterin spontaneously. The spontaneous release of neopterin was significantly decreased (p < 0.05) after supplementation with exogenous IL-2. The reverse was observed in peripheral blood mononuclear cell cultures from infection-free or control groups where relatively low neopterin secretion was markedly augmented in the presence of IL-2. The effect of IL-2 in patient cultures was unrelated to the activity of endogenous interferon gamma, because the production of this cytokine was profoundly reduced. However, IL-2-induced alterations in neopterin secretion paralleled those in the production of tumor necrosis factor alpha. This suggests that after thermal injury, biologic responses of neopterin-secreting peripheral blood mononuclear cells are directly or indirectly regulated by IL-2.

Adult↗
PubMed2006

Alterations in serum neopterin correlate with thrombolysis in myocardial infarction risk scores in acute coronary syndromes.

OBJECTIVES: Using serum neopterin as a marker of macrophage activation, we sought to examine the relationship between serum neopterin levels, thrombolysis in myocardial infarction (TIMI) risk scores, and how different treatments of acute coronary syndromes affect change in neopterin. METHODS: We examined serum neopterin concentrations at presentation and 72 h after treatment in 70 patients with acute coronary syndromes (35 with medical therapy, 25 with uncoated coronary stents, and 10 received rapamycin-eluting stents) using a commercially available immunoassay. Serum neopterin levels were determined for 36 patients with stable coronary artery disease. TIMI risk scores were calculated when appropriate (n=58). RESULTS: Serum neopterin had a strong correlation with the TIMI risk score on admission (P<0.0001). The mean baseline neopterin levels in patients with acute coronary syndromes stratified with TIMI scores between 1 and 7 were the following: patients with TIMI 1 scores had a level of 3.3+/-0.4 nmol/l, TIMI 2 patients 4.6+/-0.6 nmol/l, TIMI 3 patients 5.5+/-1.4 nmol/l, TIMI 4 patients 7.5+/-2.4 nmol/l, TIMI 5 patients 10.8+/-3.3 nmol/l, TIMI 6 patients 17.5+/-4.0 nmol/l, and TIMI 7 patients 23.0+/-7.1 nmol/l. Mean changes in serum neopterin were significantly higher for the uncoated stent group than for each of the other three groups (P<0.05). CONCLUSIONS: Serum neopterin concentrations have a high correlation with TIMI risk scores and may represent a marker useful in stratifying patients with acute coronary syndromes. Our results also suggest that the use of uncoated coronary stents results in macrophage activation not found with other treatment modalities.

Aged↗
PubMed2006

Neopterin levels during the early phase of human immunodeficiency virus, hepatitis C virus, or hepatitis B virus infection.

BACKGROUND: A study was conducted to assess the diagnostic sensitivity of neopterin screening of blood donors with regard to the detection of window-phase specimens of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In total, 1002 diagnostic window-phase specimens from 98 seroconversion panels (29 HIV-1, 52 HCV, and 17 HBV) were analyzed with viral antigen detection, viral nucleic acid amplification testing (NAT), and neopterin quantitation assays. The study was completed by the analysis of 92 anti-hepatitis B core antigen (HBc)-reactive and 103 alanine aminotransferase (ALT)-elevated blood donor specimens. RESULTS: A significant association between elevated neopterin concentrations and the very early phase of HIV-1 infection was found. No significant correlation could be observed between neopterin levels and the early phase of HCV or HBV infection. Neopterin concentration was not increased in specimens from blood donors with anti-HBc reactivity or ALT elevation. CONCLUSIONS: Neopterin screening of blood donors may identify window-phase cases of HIV, but not of HCV or HBV infection. The diagnostic sensitivity of neopterin screening during the HIV window phase is similar to that of the p24 antigen test. With the introduction of viral NATs in blood screening, there is no additional benefit of neopterin screening with regard to the three blood-borne viruses HIV, HCV, and HBV. Acute phases of other infectious agents, however, have been reported to be detected by neopterin enzyme-linked immunosorbent assays.

Alanine Transaminase↗
PubMed1999

Neopterin: a review.

Neopterin was discovered in bee larvae, in worker bees and in royal jelly. The compound was termed "neopterin" to denote that it might start a new (Greek, neo) epoch in pteridine research. Increased concentrations of neopterin were reported in patients with viral infections, suggesting that increased neopterin may originate from the immune response of patients to the infections. In vitro studies revealed that human monocytes/macrophages produce neopterin when stimulated by interferon-gamma. Neopterin can easily be detected in serum and urine. The most important clinical applications for the determination of neopterin are prognostic indicator of malignant diseases, follow-up control of chronic infections, monitoring of immune-stimulatory therapy, differential diagnosis of acute viral and bacterial infections, prognostic indicator in HIV infections and early indications of complications in allograft recipients. In recent years new physiological functions of neopterin have been discovered such as inducing or enhancing cytotoxicity, inducing apoptosis and the role of a chain breaking antioxidant. This review will focus on the immunological and physiological properties of neopterin.

Animals↗
PubMed2005

Association between neopterin and carotid intima-media thickness in hemodialysis patients.

BACKGROUND: Atherosclerotic lesions are heavily infiltrated by macrophages. Neopterin can be used as a marker of the activity of macrophages. Serum neopterin levels were elevated in non-renal patients with atherosclerosis. The intima-media thickness (IMT) of the carotid arteries in hemodialysis patients was significantly higher than in control subjects. In this study, we measured serum neopterin levels in hemodialysis patients and evaluated a possible correlation between neopterin levels and carotid IMT. PATIENTS AND METHODS: Thirty-seven hemodialysis patients (26 male/11 female, mean age 47 +/- 15 years) and 12 healthy subjects (8 male/4 female, mean age 43 +/- 10 years) were included in this study. Serum neopterin levels were measured by using a commercial ELISA kit. Carotid IMT of the subjects were measured by high-resolution B-mode ultrasonography. RESULTS: Carotid IMT values were 1.04 +/- 0.29 and 0.77 +/- 0.25 mm in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 110.9 +/- 19.1 and 3.8 +/- 2.3 ng/ml in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 103.2 +/- 21.3 ng/ml in hemodialysis patients with IMT < 1 mm (n = 15), and 116.7 +/- 15.4 ng/ml in hemodialysis patients with IMT > or = 1 mm (n = 22) (p < 0.05). Moreover, there was a significant correlation between serum neopterin levels and carotid IMT (p < 0.05, r = 0.363). CONCLUSION: Our findings suggest that neopterin could be associated with the severity of carotid atherosclerosis in hemodialysis patients.

Adult↗
PubMedDate not supplied

Urinary neopterin in patients with advanced colorectal carcinoma.

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

Adult↗
PubMed2006

Serum neopterin levels in patients with replicative and nonreplicative HBV carriers.

BACKGROUND: Infection by hepatitis B virus (HBV) causes complicated biochemical, immunological and histological changes in host immune response against the virus which can be specific or non-specific. Recent attention has focused on neopterin as a marker for the activation of cell mediated immunity. The aim of this study was to define the pattern of neopterin levels in replicative and nonreplicative HBV carriers. METHODS: Thirty HBV replicative carriers and 25 nonreplicative HBV carriers and 30 healthy adult patients were included this study. Hepatitis markers were determined by commercial kit based on chemilumminesans assay. HBV DNA was quantified by hybrid capture system. Serum neopterin levels were measured by the method of competitive enzyme-linked immunosorbent assay. Results were expressed as mean +/- SD and ranges. RESULTS: In the nonreplicative group, except for one patient, all the patients' HBeAg were negative and anti-HBe were positive. That particular patient was HBeAg positive and anti-HBe negative. In the replicative group, 23 out of 30 patients have positive HBeAg and negative anti-HBe; 7 out of 30 patients have negative HBeAg and positive anti-HBe. Serum neopterin concentrations were 14.5 +/- 10.0 (4.2-41) nmol/L in replicative HBV carriers, 8.9 +/- 4.3 (2.1-22) nmol/L in nonreplicative HBV carriers and 7.1 +/- 2.2 (4.0-12) nmol/L in the control group. Serum neopterin levels and the rates of abnormal serum neopterin levels in the replicative group were higher than the control group (P < 0.01 and P < 0.05). In the nonreplicative group, serum neopterin levels were not different from those of the control. There was a difference between replicative and nonreplicative groups in the respect of neopterin levels. CONCLUSION: In the hepatitis B infected carriers, elevated neopterin levels may be an indicator of the presence of replication.

Adolescent↗
PubMed1992

Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation.

Large amounts of D-erythro-neopterin, a pteridine derivative, are formed from guanosine triphosphate (GTP) by human macrophages upon stimulation with interferon-gamma. In addition, in humans a basal neopterin level in all body fluids is evident also in absence of immunological stimuli. Extremely high concentrations of D-erythro-neopterin were detected in biliary fluid. We therefore investigated, if an enterohepatic circulation might exist for this substance. We quantified concentrations of pteridines in serum obtained from various vessels and in biliary fluid. Samples were collected during surgery of five patients with duodenal ulcer or adenocarcinoma of the stomach. Our data clearly demonstrate the existence of an enterohepatic circulation for the recovery of neopterin which seems to be specific for this substance. The relative distributions of neopterin concentrations in the gastrointestinal tract and vessels were seen invariably in all patients and were consistent with findings in five corpses examined post mortem. In addition, significantly higher neopterin concentrations, were found in arteries than in veins. The data indicate that neopterin derivatives are consumed in the peripheral capillary system and an enterohepatic circulation is established to maintain constant blood levels of neopterin derivatives. Furthermore, we suppose that the liver is the source of constitutive neopterin concentrations.

Adenocarcinoma↗
PubMed2003

HMG-CoA reductase inhibitors are associated with decreased serum neopterin levels in stable coronary artery disease.

Neopterin, a marker of stimulated cellular immune response, is increased in unstable angina, acute myocardial infarction and possibly stable coronary artery disease. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have anti-inflammatory properties, but their effect on neopterin is largely unknown. Neopterin was measured in 232 patients undergoing elective coronary angiography and compared to the degree of atherosclerosis, use of concomitant medications and demographics. Neopterin was lower in subjects using statins (n = 66) compared to those not taking statins (median (range): 6.65 (4.1-18.3) vs. 7.70 (3.6-29.1) nmol/l, p < 0.0001). This association was also found in the subgroup of patients with coronary artery disease (1-3-vessel disease, n = 164; 6.60 (4.1-18.3) vs. 7.80 (3.6-29.1) nmol/l, p = 0.0012), whereas only a slight tendency toward lower neopterin levels was found in the group without atherosclerosis (6.90 (5.1-16.0) vs. 7.60 (4.0-18.5) nmol/l, p = 0.17). In patients with coronary atherosclerosis, neopterin concentrations were lower in smokers (n = 105) compared to non-smokers (7.20 (3.6-29.1) vs. 7.90 (4.4-18.6) nmol/l, p < 0.02), confirming previous observations. However, use of statins was associated with lower neopterin levels in both non-smokers and smokers (6.70 (4.1-18.3) vs. 7.60 (3.6-29.1) nmol/l, p < 0.05, and 6.20 (5.2-16.0) vs. 7.80 (4.4-18.6) nmol/l, p < 0.05, respectively). Overall, similar serum neopterin concentrations were found in patients with coronary atherosclerosis and those without. In accordance with their anti-inflammatory effects, the use of statins is associated with lower neopterin levels in patients undergoing elective coronary angiography.

Adult↗
PubMed1996

Neopterin in acute pancreatitis.

BACKGROUND: Activation of the cellular immune system may play a role in the pathogenesis of acute pancreatitis (AP); it has recently been proposed that excessive leukocyte stimulation may lead to the most severe forms of AP. The aim of this study was to investigate serum neopterin, a useful in vivo marker of macrophage activation, in mild and severe AP and its relationship with other markers of leukocyte activation, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). METHODS: Serum levels of neopterin (mmol/ml), IL-6 (pg/ml), and TNF (pg/ml) were measured on the 1st and 7th day of hospitalization in 17 patients with severe AP and 24 with mild AP. Severe AP was defined in accordance with the Atlanta criteria: all patients have necrosis at contrast-enhanced computerized tomography scan. RESULTS: Day 1: Neopterin and IL-6 levels were significantly higher in severe than in mild AP and normal controls; mild AP values were also significantly higher than in normal controls. The best neopterin cutoff level we obtained (30 mmol/ml) reached a specificity of 76% and a sensitivity of 46% in distinguishing severe from mild AP. Day 7: Neopterin was significantly higher in severe AP than in mild AP and in normal controls; no difference was seen between mild AP values and normal controls; neopterin serum levels were significantly higher on day 7 than on day 1 in severe AP but not in mild AP; in both groups of patients IL-6 was significantly higher on day 1 than on day 7. Using a neopterin cutoff level of 40 mmol/ml, we found specificity and sensitivity value of 92% in differentiating severe from mild AP. With regard to TNF values, no difference was seen on day 1 and 7 in the two groups of patients in comparison with normal controls. Neopterin serum values did not correlate with IL-6 and TNF on either day. CONCLUSIONS: These results confirm the activation of the cellular immune system in AP. Initially enhanced NEOP and IL-6 serum levels reflect the severity of the disease; neopterin may be considered a reliable prognostic indicator also at a distance from AP onset because its levels increase during the 1st week of AP in patients with severe forms only.

Acute Disease↗
PubMed1997

[Urinary neopterin levels in patients with genitourinary tract malignancies].

BACKGROUND: Neopterin is released from macrophages upon stimulation with gamma-interferon, secreted by activated T cell. Therefore it has been recognized as a useful indicator of the activation of the T cell-macrophage system. Increased neopterin levels are observed in patients with acute graft rejections, viral infections, auto-immune diseases and several malignancies. Urinary neopterin concentrations were determined in patients with genitourinary tract malignancies to evaluate the usefulness of neopterin as a tumor marker. METHODS: Urinary neopterin concentrations were determined by high-performance liquid chromatography in 90 patients with genitourinary tract malignancies and 28 patients with benign urological tumors and 34 healthy subjects. RESULTS: Increased urinary neopterin levels were observed in 52% of the patients with genitourinary tract malignancies and 7% with benign urological tumors. The positivity rate in patients with renal cell carcinoma (RCC), renal pelvic and ureteral tumor, bladder tumor (BT), prostatic carcinoma (PC) and testicular tumor was 68%, 80%, 47% and 30%, respectively. The difference in the urinary neopterin levels between low and high stages was highly significant (p < 0.0005) in patients with RCC (stage I-II vs. stage III-IV) and BT (T1S-1 VS. T2-4). The urinary neopterin levels were also correlated with the tumor grade in patients with RCC and PC. CONCLUSION: Our study suggests that urinary neopterin levels may supplement laboratory examinations for patients with genitourinary tract malignancies, providing useful information in evaluating the tumor stage and follow-up of the disease.

Adult↗
PubMedDate not supplied

Increased neopterin concentrations in patients with cancer: indicator of oxidative stress?

In vitro, large amounts of neopterin are produced by human monocytes/macrophages upon stimulation with interferon-gamma. In vivo increased neopterin concentrations in human serum and urine indicate activation of cell-mediated (Th1-type) immune response, e.g., during virus infections, autoimmune diseases, allograft rejection and in certain types of malignancy. In various groups of patients with malignant diseases neopterin concentrations correlate to the stage of disease, and higher neopterin concentrations in serum, urine or ascitic fluid were shown to significantly predict worse prognosis regarding relapse and survival. The amounts of neopterin produced by activated monocytes/macrophages correlate with their capacity to release reactive oxygen species (ROS). With this background, neopterin concentrations in body fluids can be regarded as an indirect estimate of the degree of oxidative stress emerging during cell-mediated immune response. Moreover, recently neopterin was found itself to be capable of enhancing toxic effects induced by ROS. In vitro, neopterin derivatives were able to interfere with intracellular signal transduction pathways involved in, e.g., programmed cell death and the induction of proto-oncogene c-fos or nuclear factor-chi B. The data support the view that increased production of ROS--indicated by increased neopterin concentrations--could modulate the development, the proliferation and the survival of malignant cells.

Anemia↗
PubMedDate not supplied

[Serum neopterin in hepatitis B].

Activation of the immunity system commonly followed the development of viral diseases. Neopterin is evidently a marker of the activation. Elevation of neopterin levels in AIDS and tumor patients correlates with the severity of the disease. Radioimmunoassay of neopterin content was performed in the sera of 11 patients with virus B hepatitis (6 patients with its acute pattern, 3 with its acute pattern concurrent with delta-infection and 2 subjects with chronic active virus B hepatitis). Mean neopterin content in the sera of virus B hepatitis patients was 19.9 +/- 5.7 nM/l being significantly higher than that in donors (5.0 +/- 0.8 nM/l) (p less than 0.001). In this line neopterin levels higher than 9 nM/l (the upper normal limits) were identified in 63% of the patients. Mean content of beta-2-microglobulin in hepatitis patients was 3.3 +/- 0.53 mg/l being significantly different from that in donors (1.8 +/- 0.3 mg/l) (p less than 0.05). Association between higher neopterin levels and the severity of the disease was fully proved clinically, with the exception of the two expired persons whose neopterin levels were within normal limits. The data obtained evidenced an increase in neopterin levels associated with virus B hepatitis. It widened the understanding of the disease pathogenesis and permitted the determination of neopterin levels be used in correlation with clinical data as a prognostic value for the course of the disease.

Adult↗
PubMed1991

[The clinical importance of the dynamic determination of the serum neopterin level in patients with dilated cardiomyopathy].

Serum neopterin was measured over time (from 3 to 24 months) by RIA in 15 patients with dilated cardiomyopathy. Comparison with the clinical data revealed that the initially normal concentration of neopterin (less than 9 nM/l) was associated with a stable disease course on a long-term observation (group I). The second group with an initially high neopterin concentration showed an objective improvement of the health status together with normalization of the neopterin level. The third group of patients were characterized by an increase of the neopterin level measured over time, coupled with a disease progress. It should be noted that 5 out of 8 patients died. In addition to neopterin measurements, the patients with dilated cardiomyopathy were examined for serum beta-2-microglobulin (beta-2M). Analysis of the data obtained has demonstrated a similar relationship between the level of neopterin and beta-2M and the clinical course of dilated cardiomyopathy. Still, neopterin is a more sensitive marker. Therefore, the data obtained attest to a possibility of the use of serum neopterin as a prognostic marker in patients suffering from dilated cardiomyopathy.

Adolescent↗
PubMedDate not supplied

[Blood levels of neopterin in patients with liver cirrhosis].

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune diseases and different malignancies. Recently, increased urinary neopterin levels have been found in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels were measured in 23 cirrhotic patients (6 HBV related, 7 alcoholic and 10 cryptogenetic cirrhosis) and in 24 normal subjects. Mean values of serum neopterin were statistically increased in cirrhotics (3.92 +/- 3.28 ng/mL versus 1.24 +/- 0.51 ng/mL in controls, p less than 0.01). Serum neopterin values were not statistically different either in cirrhotics assessed in three different classes according to Child's classification or in cirrhotics with or without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with serum aspartate and alanine aminotransferases, alkaline phosphatase, gamma-glutamyltransferase and gammaglobulins values. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the histological activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all forms and in all stages of liver cirrhosis.

Adult↗
PubMed1989

Neopterin: a predictive marker of acquired immune deficiency syndrome in human immunodeficiency virus infection.

In 79 homosexual men infected with human immunodeficiency virus (HIV), urinary neopterin was significantly higher as compared with 70 HIV-seronegative men in the same cohort (p less than 0.0001). This highly significant association was found both for naturally occurring oxidized (native) neopterin and for total neopterin (native plus chemically oxidized forms). In prospective follow-up for 18 months, the odds that the acquired immune deficiency syndrome (AIDS) would develop were elevated 25-fold among those whose native neopterin levels were in the highest quartile compared with those with lower neopterin levels, and the corresponding odds ratio for total neopterin was 7.8. Logistic regression analyses indicated that neopterin added useful information to T4-cell count in predicting AIDS onset and that both are statistically significant in the multivariate model. A cross-sectional survey revealed that neopterin levels were correlated with number of receptive anal intercourse partners in the year before HIV seroconversion (r = 0.60, p = 0.0005). Since neopterin may serve as a marker of monocyte/macrophage activation by soluble factors such as gamma-interferon, these data support a growing body of virologic and immunologic evidence that highlights the important role of the monocyte/macrophage in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗