In the pathogenesis of Alzheimer disease (AD), it has been proposed that the anti-inflammatory interleukins such as IL-10 regulate β-amyloid-induced microglial inflammatory responses inhibiting the proinflammatory cytokine IL-6. Since the promoters of the IL-10 and IL-6 genes show single nucleotide polymorphisms (SNPs) (IL-10: -1082 G→A; IL-6: -174 G→C), we investigated these SNPs and cytokine production by peripheral blood mononuclear cells in 65 AD patients and 65 controls (HC). In AD there was a significant increase of the -1082A IL-10 allele (P=0.009) and a decrease of -1082GG genotype (P=0.019). The frequency of the GG IL-6 genotype in AD was lower and the C allele significantly higher (P<0.005). The co-occurrence of IL-10 A and IL-6 C alleles significantly raised the odds ratio (OR 11.2, confidence interval: CI 1.3-97.3; P<0.05) independently of apolipoprotein E4 (adjusted OR 10.3, CI 1-108; P<0.05). Only amyloid-stimulated IL-10 production differed between the groups (P=0.023). These results raise questions regarding the inflammatory theory in AD, pointing to a pivotal role of IL-10 and IL-6 and a selective alteration in this network.
Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease / B. Arosio, D. Trabattoni, L. Galimberti, P. Bucciarelli, F. Fasano, C. Calabresi, C.L. Cazzullo, C. Vergani, G. Annoni, M. Clerici. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 25:8(2004), pp. 1009-1015.
|Titolo:||Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease|
AROSIO, BEATRICE (Primo)
TRABATTONI, DARIA LUCIA (Secondo)
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||Alzheimer's disease; Apolipoprotein E; Inflammation; Interleukin-10; Interleukin-6; Single nucleotide polymorphism; T lymphocytes|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neurobiolaging.2003.10.009|
|Appare nelle tipologie:||01 - Articolo su periodico|