RESUMEN
The study evaluates the expression and production of cytokines in peripheral blood mononuclear cells of patients with Alzheimer disease treated or not treated with acetylcholinesterase inhibitor, which enhances neuronal transmission. Cytokines associated with brain inflammation such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha have been implicated in the regulation of amyloid peptide protein synthesis. The anti-inflammatory cytokine, IL-4, may suppress the activity of IL-1beta. Patients were assessed for clinical and immunologic features at baseline and after 1 month of treatment with Donepezil, an acetylcholinesterase inhibitor. Peripheral blood mononuclear cells were cultured with and without phytohemagglutinin stimulation. IL-1beta and IL-4 levels were measured by enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to determine the expression of cytokines in peripheral mononuclear cells. Compared with untreated patients and healthy control subjects, IL-1beta levels and expression decreased in Alzheimer disease patients treated with Donepezil (P < 0.001). In contrast, IL-4 levels and expression were significantly higher in Alzheimer patients treated with the acetylcholinesterase inhibitor. This increment was observed in both unstimulated and phytohemagglutinin-stimulated peripheral blood mononuclear cells.
Asunto(s)
Enfermedad de Alzheimer/sangre , Inhibidores de la Colinesterasa/farmacología , Interleucina-1/biosíntesis , Interleucina-4/biosíntesis , Leucocitos Mononucleares/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Células Cultivadas , Inhibidores de la Colinesterasa/uso terapéutico , Donepezilo , Femenino , Humanos , Indanos/farmacología , Indanos/uso terapéutico , Interleucina-1/antagonistas & inhibidores , Interleucina-1/sangre , Interleucina-4/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Piperidinas/farmacología , Piperidinas/uso terapéuticoRESUMEN
Elevated levels of cytokines have been detected in brains of Alzheimer's disease (AD) patients, and altered peripheral levels of IL-1beta, TNFalpha and IL-6 have been reported in these patients. We studied the ability of PBMC from patients with AD, matched with a control group, to release pro- and anti-inflammatory cytokines, and the effect of AChEI treatment on cytokine release. Our data indicates that AChEI treatment down-regulates IL-1, IL-6 and TNF, and up-regulates the expression and production of IL-4 in PBMC in AD patients, and that AChEI leads to the remodelling of the cytokine network, probably acting on the lymphocytic cholinergic system.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Citocinas/metabolismo , Expresión Génica/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Citocinas/genética , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inflamación/tratamiento farmacológico , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
OBJECTIVE: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS. METHODS: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the -491 A/T polymorphism of the APOE promoter were determined. RESULTS: No association was observed between the APOE epsilon4 allele and clinical characteristics of our study population. We also investigated the -491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the -491 A/T polymorphism and the selected clinical variables. CONCLUSIONS: In our population the APOE epsilon4 allele and the -491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS.
