RESUMEN
Neopterin, a low-molecular-mass pteridine produced by macrophages, is closely associated with activation of the cellular immune system. Neopterin biosynthesis during inflammatory disease is primarily derived from interferon-activated monocytes/macrophages and neopterin concentrations may be significantly increased in a particular disease state compared to controls. A follow-up of serum neopterin concentrations during the course of an infectious disease could be useful for measuring the activity of the disease and the influence of treatment. We have developed a simple dipstick assay for the semi-quantitative detection of the neopterin concentration in the serum of patients during the course of an infectious disease. Assay performance was comparable to an ELISA, but there is no requirement for specialised equipment.
Asunto(s)
Bioensayo/métodos , Neopterin/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , HumanosRESUMEN
Neopterin, a product of gamma-interferon-activated macrophages, was measured in sera from 28 patients (12 patients with cutaneous leishmaniasis and 16 patients with visceral leishmaniasis) to determine the utility as a marker of disease activity and therapeutic efficacy. Patients originated from Kenya (n=5) and from the Academic Medical Center, Amsterdam, The Netherlands (n=23). In seven patients follow-up sera after treatment were available. Two patients at the time of diagnosis of visceral leishmaniasis were co-infected with HIV. The 12 patients with cutaneous leishmaniasis had serum neopterin levels below the upper limit of the normal range. All 16 patients with visceral leishmaniasis had elevated levels of serum neopterin before treatment. In six out of seven patients with visceral leishmaniasis followed during treatment neopterin levels decreased to values below the upper limit of the normal range (10 nmol l(-1)). Sequential measurements of serum neopterin levels may be useful for monitoring therapeutic efficacy in patients with visceral leishmaniasis.
Asunto(s)
Gluconato de Sodio Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Visceral/tratamiento farmacológico , Neopterin/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Humanos , Leishmaniasis Cutánea/sangre , Leishmaniasis Cutánea/patología , Leishmaniasis Visceral/sangre , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/patología , Masculino , Persona de Mediana Edad , Pentamidina/uso terapéutico , Resultado del TratamientoRESUMEN
Reactions, a relatively common phenomenon among leprosy patients in treatment, require early detection and proper management to prevent serious sequelae. It is generally accepted that reactional states are immunologically mediated and, as such, usually improve with immunomodulatory treatments such as corticosteroids or thalidomide. Neopterin, a product of gamma-interferon-activated macrophages, is a marker for cell-mediated immune activation and may be useful to detect reactional states in leprosy. Here, we compared neopterin levels in single serum samples from leprosy patients with and without reaction with untreated controls and, when available, serial samples among patients with and without reaction. Levels in the single sample measurements, conducted in 22 patients with a reversal reaction (mean 14.5 nmol l(-1), S.D. 8.7) and 13 with erythema nodosum leprosum (mean 16.9 nmol l(-1), S.D. 13.6), were significantly higher (P=0.02 and P=0.001, respectively) than levels in 26 untreated patients (mean 9.1 nmol l(-1), S.D. 7.3). Values above the upper limit of normal (10 nmol l(-1)) were found in seven of 26 untreated patients, 14 of the 22 reversal reaction patients (P=0.01) and 10 of the 13 ENL patients (P=0.003). Serial serum samples, obtained from six patients that developed reactions and 14 that remained free of reaction, indicated that reversal reaction or erythema nodosum leprosum paralleled a concomitant increase in the serum neopterin level. Neopterin levels generally declined upon corticosteroid therapy. Neopterin may be a useful marker for reactional states in leprosy by providing a laboratory parameter to assess the onset, progression, response to therapy and resolution.
Asunto(s)
Biomarcadores/sangre , Lepra/sangre , Neopterin/sangre , Eritema Nudoso/sangre , HumanosRESUMEN
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.