Circulating Monocytes Exhibit an Endotoxin Tolerance Status after Acute Ischemic Stroke: Mitochondrial DNA as a Putative Explanation for Poststroke Infections
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Hernandez-Jimenez, Enrique; Gutiérrez-Fernández, María; Cubillos-Zapata, Carolina; Otero-Ortega, Laura; Rodríguez-Frutos, Berta; [et al.]Fecha
2017-03-01Resumen
Patients with acute ischemic stroke (AIS) suffer from infections associated with mortality. The relevance of the innate immune system, and monocytes in particular, has emerged as an important factor in the evolution of these infections. The study enrolled 14 patients with AIS, without previous treatment, and 10 healthy controls. In the present study, we show that monocytes from patients with AIS exhibit a refractory state or endotoxin tolerance. The patients were unable to orchestrate an inflammatory response against LPS and expressed three factors reported to control the evolution of human monocytes into a refractory state: IL-1R-associated kinase-M, NFkB2/p100, and hypoxia-inducible factor-1α. The levels of circulating mitochondrial DNA (mtDNA) in patients with AIS correlated with impaired inflammatory response of isolated monocytes. Interestingly, the patients could be classified into two groups: those who were infected and those who were not, according to circulating mtDNA levels. ...
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Circulating Monocytes, tolerance, stroke