PMID- 16730447
OWN - NLM
STAT- MEDLINE
DCOM- 20060816
LR  - 20220311
IS  - 1010-7940 (Print)
IS  - 1010-7940 (Linking)
VI  - 30
IP  - 1
DP  - 2006 Jul
TI  - Hyporesponsiveness of T cell subsets after cardiac surgery: a product of altered 
      cell function or merely a result of absolute cell count changes in peripheral 
      blood?
PG  - 64-71
AB  - OBJECTIVE: The activity of the specific immune system and especially the function 
      of T helper (TH) cells are reduced after cardiac surgery. This decrease is 
      followed by an increase in TH2 cell activity and a delayed recovery of TH1 cell 
      function (TH1/TH2 shift). Neither the underlying cause nor the relationship 
      between the absolute numbers of T lymphocyte subpopulations, the state of 
      activation of these cells and cytokine synthesis in cell culture has been 
      clarified. We conducted a prospective study in order to test the hypothesis that 
      the decrease in specific immunity is not caused by dilution effects but by 
      functional alterations in T cell subsets. METHODS: Blood samples were obtained 
      from 40 patients undergoing elective cardiac surgery with cardiopulmonary bypass 
      (CPB) preoperatively (d0), immediately after surgery (dx), and on the 1st (d1), 
      3rd (d3) and 5th (d5) postoperative days. The samples were stimulated for 24h 
      with staphylococcal enterotoxin B and lipopolysaccharide. Interferon (IFN)-gamma, 
      interleukin (IL)-2, IL-4, and IL-5 concentrations were measured by flow cytometry 
      using a cytokine bead array kit. We determined white blood cell counts, analysed 
      lymphocyte populations, and assayed human leukocyte antigen (HLA)-DR expression 
      on cluster of differentiation (CD)4+ and CD8+ lymphocytes. Cytokine 
      concentrations were corrected to preoperative absolute numbers of T helper cells. 
      RESULTS: Leukocyte counts were elevated during the entire postoperative course 
      with a maximum on dx. Absolute lymphocyte counts and especially the T cell 
      subpopulations significantly increased immediately after surgery, then decreased 
      to a minimum on d1 and increased again until they returned to preoperative levels 
      on d3. The release of IFN-gamma, IL-2 and IL-4 was significantly reduced from dx 
      to d5 with a minimum on d1. IL-5 was significantly reduced on dx and d1. When the 
      concentrations were corrected to preoperative TH lymphocyte levels, IL-2 and IL-5 
      synthesis was significantly reduced only on dx and IL-4 release only on dx and 
      d1. By contrast, IFN-gamma synthesis decreased postoperatively and remained 
      suppressed until d5 with a minimum on d1. Only on d1 did an increase in HLA-DR 
      expression give evidence of a change in the state of TH cell activation. 
      CONCLUSIONS: The number of immune cells of the specific and the non-specific 
      immune system is not reduced in the immediate postoperative period. Haemodilution 
      thus has no detectable effect on immune function at this time point. Beginning on 
      d1, the function of specific immune cells, especially TH lymphocytes, is severely 
      suppressed. This functional alteration appears not to be preceded by T cell 
      activation during CPB. Although TH cell activity begins to increase on d1, 
      cytokine synthesis is reduced. When cytokine synthesis is corrected to the 
      absolute number of TH cells in culture, there is strong evidence for an increase 
      in TH2 cell activity. On the whole, these results corroborate the hypothesis of a 
      TH1/TH2 shift that is primarily caused by an alteration of TH1 function. Neither 
      haemodilution nor a preceding activation plays a major role.
FAU - Franke, Axel
AU  - Franke A
AD  - Department of Cardiovascular Surgery, Bundeswehr Central Hospital, Rubenacher 
      Str. 170, D 56072 Koblenz, Germany. axel1franke@bundeswehr.org
FAU - Lante, Wolfgang
AU  - Lante W
FAU - Kurig, Edmond
AU  - Kurig E
FAU - Zoller, Lothar G
AU  - Zoller LG
FAU - Weinhold, Christian
AU  - Weinhold C
FAU - Markewitz, Andreas
AU  - Markewitz A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060526
PL  - Germany
TA  - Eur J Cardiothorac Surg
JT  - European journal of cardio-thoracic surgery : official journal of the European 
      Association for Cardio-thoracic Surgery
JID - 8804069
RN  - 0 (Cytokines)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Hemoglobins)
SB  - IM
MH  - Aged
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - *Cardiac Surgical Procedures
MH  - Cardiopulmonary Bypass
MH  - Cytokines/blood
MH  - Female
MH  - HLA-DR Antigens/blood
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - *Immune Tolerance
MH  - Immunophenotyping
MH  - Leukocyte Count
MH  - Lymphocyte Activation
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Postoperative Period
MH  - Prospective Studies
MH  - T-Lymphocyte Subsets/*immunology
EDAT- 2006/05/30 09:00
MHDA- 2006/08/17 09:00
CRDT- 2006/05/30 09:00
PHST- 2005/11/06 00:00 [received]
PHST- 2006/02/20 00:00 [revised]
PHST- 2006/03/03 00:00 [accepted]
PHST- 2006/05/30 09:00 [pubmed]
PHST- 2006/08/17 09:00 [medline]
PHST- 2006/05/30 09:00 [entrez]
AID - S1010-7940(06)00298-3 [pii]
AID - 10.1016/j.ejcts.2006.03.029 [doi]
PST - ppublish
SO  - Eur J Cardiothorac Surg. 2006 Jul;30(1):64-71. doi: 10.1016/j.ejcts.2006.03.029. 
      Epub 2006 May 26.