title: CD62L (L-selectin) shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.
abstract: OBJECTIVE
  To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.
  
  
  METHODS
  Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.
  
  
  RESULTS
  25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p ≤ 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401).
  
  
  CONCLUSIONS
  Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes.
authors.affiliation: University Department of Anesthesiology and Pain Therapy, Inselspital, Bern University Hospital, Bern, Switzerland. gabor.erdoes@insel.ch
authors.forename: Gabor
authors.initials: G
authors.lastname: Erdoes
authors.forename: Maria L
authors.initials: ML
authors.lastname: Balmer
authors.forename: Emma
authors.initials: E
authors.lastname: Slack
authors.forename: Istvan
authors.initials: I
authors.lastname: Kocsis
authors.forename: Lutz E
authors.initials: LE
authors.lastname: Lehmann
authors.forename: Balthasar
authors.initials: B
authors.lastname: Eberle
authors.forename: Frank
authors.initials: F
authors.lastname: Stüber
authors.forename: Malte
authors.initials: M
authors.lastname: Book
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000368:Aged; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006331:Heart Diseases / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D019041:L-Selectin / Q000097:blood*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013211:Staphylococcus aureus / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006684:HLA-DR Antigens; D016209:Interleukin-8; D008024:Ligands; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; C009900:lipoteichoic acid; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human