title: 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?
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Bundeswehr Central Hospital, Rübenacher Str. 170, D 56072 Koblenz, Germany. axel1franke@bundeswehr.org
authors.forename: Axel
authors.initials: A
authors.lastname: Franke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lante
authors.forename: Edmond
authors.initials: E
authors.lastname: Kurig
authors.forename: Lothar G
authors.initials: LG
authors.lastname: Zöller
authors.forename: Christian
authors.initials: C
authors.lastname: Weinhold
authors.forename: Andreas
authors.initials: A
authors.lastname: Markewitz
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D016207:Cytokines / Q000097:blood; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D006454:Hemoglobins