PMID- 31545153
OWN - NLM
STAT- MEDLINE
DCOM- 20201019
LR  - 20201019
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 127
IP  - 6
DP  - 2019 Dec 1
TI  - Early suppression of peripheral mononuclear blood cells in sepsis in response to 
      stimulation with cytomegalovirus, OKT3, and pokeweed mitogen.
PG  - 1539-1547
LID - 10.1152/japplphysiol.00438.2019 [doi]
AB  - Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms 
      may prevail. Whether functional tests are helpful to detect immune alterations is 
      largely unknown. Therefore, we tested the hypotheses that reactivity of 
      peripheral blood mononuclear cells (PBMCs) to secrete interferon-gamma (IFNgamma) 
      following stimulation in vitro is decreased in patients with early sepsis 
      compared with postoperative patients. IFNgamma secretion [enzyme-linked immunospot 
      (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed 
      mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen 
      (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [days 
      1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients 
      with sepsis (n = 7) and patients undergoing major abdominal surgery (radical 
      prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was 
      assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy 
      volunteers (German clinical trials database no. 00007694). In patients with 
      sepsis, IFNgamma secretion (ELISpot) was decreased compared with controls after 
      stimulation with CMV (P = 0.01), OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), 
      whereas unstimulated IFNgamma secretion did not differ. HLA-DRA expression was also 
      significantly decreased in patients with sepsis at all time points (P = 0.004) 
      compared with postoperative surgical patients, a finding confirmed in the larger 
      cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as 
      HLA-DRA expression was already decreased upon ICU admission in patients with 
      sepsis when compared with postoperative controls, suggesting early depression of 
      acquired immunity. ELISpot assays may help to clinically characterize the time 
      course of immunocompetence in patients with sepsis.NEW & NOTEWORTHY We observed 
      suppression of reactivity to stimulation with cytomegalovirus, 
      muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients 
      with early sepsis when compared with postoperative controls. Thus, there is early 
      depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may 
      help to characterize immunocompetence in patients with sepsis.
FAU - Malewicz, N M
AU  - Malewicz NM
AUID- ORCID: 0000-0002-9045-203X
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Walstein, K
AU  - Walstein K
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Heine, T
AU  - Heine T
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Engler, A
AU  - Engler A
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Bick, A
AU  - Bick A
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Cox, L
AU  - Cox L
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Dotsch, A
AU  - Dotsch A
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Westendorf, A M
AU  - Westendorf AM
AD  - Institute for Medical Microbiology, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Horn, P A
AU  - Horn PA
AD  - Institute for Transfusion Medicine, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Lindemann, M
AU  - Lindemann M
AD  - Institute for Transfusion Medicine, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Peters, J
AU  - Peters J
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
FAU - Schafer, S T
AU  - Schafer ST
AD  - Klinik fur Anasthesiologie und Intensivmedizin, Universitat Duisburg-Essen & 
      Universitatsklinikum, Essen, Germany.
AD  - Department of Anaesthesiology, Klinikum der Universitat Munchen, 
      Ludwig-Maximilians-Universitat Munchen, Munich, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190923
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Muromonab-CD3)
RN  - 0 (Pokeweed Mitogens)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cytomegalovirus/*pathogenicity
MH  - Female
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Leukocytes, Mononuclear/*drug effects/*virology
MH  - Male
MH  - Middle Aged
MH  - Muromonab-CD3/*pharmacology
MH  - Pokeweed Mitogens/*pharmacology
MH  - Sepsis/*drug therapy/*virology
OTO - NOTNLM
OT  - CMV
OT  - ELISpot
OT  - HLA-DR
OT  - IFNgamma secretion
OT  - sepsis
EDAT- 2019/09/24 06:00
MHDA- 2020/10/21 06:00
CRDT- 2019/09/24 06:00
PHST- 2019/09/24 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/09/24 06:00 [entrez]
AID - 10.1152/japplphysiol.00438.2019 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2019 Dec 1;127(6):1539-1547. doi: 
      10.1152/japplphysiol.00438.2019. Epub 2019 Sep 23.