PMID- 19604380
OWN - NLM
STAT- MEDLINE
DCOM- 20100128
LR  - 20220330
IS  - 1466-609X (Electronic)
IS  - 1364-8535 (Print)
IS  - 1364-8535 (Linking)
VI  - 13
IP  - 4
DP  - 2009
TI  - Phenotype changes and impaired function of dendritic cell subsets in patients 
      with sepsis: a prospective observational analysis.
PG  - R119
LID - 10.1186/cc7969 [doi]
AB  - INTRODUCTION: Patients 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. METHODS: In 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. RESULTS: At baseline, a profound 
      reduction in the numbers of myeloid DCs (MDCs), plasmacytoid DCs (PDCs), and 
      CD14dimCD16positive monocytes was observed in sepsis whereas 
      CD14brightCD16negative and CD14brightCD16positive 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. IFNalpha 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. CONCLUSIONS: In 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.
FAU - Poehlmann, Holger
AU  - Poehlmann H
AD  - Department of Medical Immunology, Charite Universitatsmedizin Berlin, Campus 
      Mitte, Chariteplatz 1, Berlin 10117, Germany. holger.poehlmann@charite.de
FAU - Schefold, Joerg C
AU  - Schefold JC
FAU - Zuckermann-Becker, Heidrun
AU  - Zuckermann-Becker H
FAU - Volk, Hans-Dieter
AU  - Volk HD
FAU - Meisel, Christian
AU  - Meisel C
LA  - eng
PT  - Journal Article
DEP - 20090715
PL  - England
TA  - Crit Care
JT  - Critical care (London, England)
JID - 9801902
RN  - 0 (Cytokines)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cytokines/metabolism
MH  - Dendritic Cells/immunology/metabolism/*pathology
MH  - Female
MH  - Flow Cytometry
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Prospective Studies
MH  - Sepsis/*pathology
PMC - PMC2750167
EDAT- 2009/07/17 09:00
MHDA- 2010/01/29 06:00
PMCR- 2009/07/15
CRDT- 2009/07/17 09:00
PHST- 2009/03/19 00:00 [received]
PHST- 2009/06/10 00:00 [revised]
PHST- 2009/07/15 00:00 [accepted]
PHST- 2009/07/17 09:00 [entrez]
PHST- 2009/07/17 09:00 [pubmed]
PHST- 2010/01/29 06:00 [medline]
PHST- 2009/07/15 00:00 [pmc-release]
AID - cc7969 [pii]
AID - 10.1186/cc7969 [doi]
PST - ppublish
SO  - Crit Care. 2009;13(4):R119. doi: 10.1186/cc7969. Epub 2009 Jul 15.