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Critical Care

, 13:R119

First Online: 15 July 2009Received: 19 March 2009Accepted: 15 July 2009

Abstract

IntroductionPatients with sepsis often demonstrate severely impaired immune responses. The hallmark of this state of immunoparalysis is monocytic deactivation characterized by decreased human leukocyte antigen HLA-DR expression and reduced production of proinflammatory cytokines. Recently, diminished numbers of dendritic cells DCs were reported in patients with sepsis. However, little is known about DC phenotype and function in human sepsis. We therefore compared phenotypic and functional changes in monocyte and DC subsets in patients with sepsis and immunoparalysis.

MethodsIn a prospective observational analysis, 16 consecutive patients with severe sepsis and septic shock age 59.2 ± 9.7 years, 13 male, Sequential Organ Failure Assessment score 6.1 ± 2.7 and immunoparalysis monocytic HLA-DR expression < 5,000 antibodies-cell and 16 healthy volunteers were included. Peripheral blood DC counts, HLA-DR expression and ex vivo cytokine production were evaluated in comparison with monocyte subsets over time.

ResultsAt baseline, a profound reduction in the numbers of myeloid DCs MDCs, plasmacytoid DCs PDCs, and CD14CD16 monocytes was observed in sepsis whereas CD14CD16 and CD14CD16 monocyte numbers were increased. HLA-DR expression was reduced on all monocyte and DC subsets. Production of proinflammatory cytokines and intracellular cytokine staining in response to lipopolysaccharide and lipoteichoic acid was impaired in monocyte subsets and MDCs, whereas IL-10 secretion was increased. IFNα response by stimulated PDCs was significantly decreased compared with controls. At day 28, HLA-DR expression and cytokine production of DC and monocyte subsets remained lower in septic patients compared with controls.

ConclusionsIn sepsis, long-lasting functional deactivation is common to all circulating monocyte and DC subsets. In addition to decreased peripheral blood DC counts, functional impairment of antigen-presenting cells may contribute to an impaired antimicrobial defense in sepsis.

AbbreviationsAPCantigen-presenting cell

DCdendritic cell

ELISAenzyme-linked immunosorbent assay

FITCFluoresceinisothiocyanat

HLAhuman leukocyte antigen

IFNinterferon

ILinterleukin

LPSlipopolysaccharide or endotoxin

LTAlipoteichoic acid

MDCmyeloid dendritic cell

ODNoligonucleotides

PDCplasmacytoid dendritic cell

PEphycoerythrin

TLRToll-like receptor

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-cc7969 contains supplementary material, which is available to authorized users.

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Autor: Holger Poehlmann - Joerg C Schefold - Heidrun Zuckermann-Becker - Hans-Dieter Volk - Christian Meisel

Fuente: https://link.springer.com/



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