title: Interleukin-10. A role in the development of postoperative immunosuppression.
abstract: BACKGROUND
  The cause of diminished monocyte major histocompatibility complex class II antigen expression after surgery or trauma is unclear. Interleukin-10 (IL-10) regulates inflammatory cytokine production and major histocompatibility complex class II (HLA-DR) expression in vitro.
  
  
  OBJECTIVE
  To quantify in vivo IL-10 messenger RNA (mRNA) and protein and monocyte HLA-DR expression after major surgery and to investigate the effects of IL-10 neutralizing blockade on monocyte HLA-DR expression in vitro.
  
  
  METHODS
  Inception cohort study of 48 surgical patients from preoperative status to postoperative day 7 and 9 healthy volunteers (controls).
  
  
  METHODS
  Large teaching hospital, Northern England.
  
  
  METHODS
  Monocyte HLA-DR and cytokine mRNA expression was determined in 32 of 48 consecutive patients undergoing elective major resectional surgery. Mononuclear cells for in vitro studies and serum samples for IL-10 measurement were obtained from the remaining 16 patients.
  
  
  METHODS
  Monocyte HLA-DR expression determined by flow cytometry, IL-10, and tumor necrosis factor mRNA in peripheral blood mononuclear cells assayed by multiplex reverse transcriptase polymerase chain reaction, and serum IL-10 determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Monocyte HLA-DR expression (in mean channel fluorescence units [MCF]) was significantly reduced 24 hours after surgery (MCF [+/- SEM], 32.6 +/- 2.3 vs 16.3 +/- 1.2; P < .001) and remained low during the first postoperative week. A relative increase in IL-10 to G3PDH mRNA ratio (mean [+/- SEM], 0.95 +/- 0.08 vs 0.59 +/- 0.06; P < .01) and serum IL-10 (mean [+/- SEM], 18.1 +/- 4.1 vs 5.4 +/- 0.8 pg/mL; P < .01) was noted on the first postoperative day. A significant correlation existed between HLA-DR antigen expression and the presence of IL-10 mRNA transcript on the first postoperative day (P < .01). Lipopolysaccharide-induced up-regulation of monocyte HLA-DR expression was significantly impaired on the first postoperative day (mean [+/- SEM], 151% +/- 24.4% vs 60% +/- 10.1%; P < .01), but this was partially reversed by IL-10 neutralizing antibody (mean [+/- SEM], 60% +/- 10.1% vs 115% +/- 11.6%; P < .01).
  
  
  CONCLUSIONS
  Interleukin-10 gene expression correlates with the fall in monocyte HLA-DR antigen expression in patients undergoing major abdominal surgery and may account for the immunosuppression associated with surgical injury.
authors.affiliation: Academic Unit of Surgery, St Jame's University Hospital, Leeds, England.
authors.forename: A
authors.initials: A
authors.lastname: Klava
authors.forename: A C
authors.initials: AC
authors.lastname: Windsor
authors.forename: S M
authors.initials: SM
authors.lastname: Farmery
authors.forename: L F
authors.initials: LF
authors.lastname: Woodhouse
authors.forename: J V
authors.initials: JV
authors.lastname: Reynolds
authors.forename: C W
authors.initials: CW
authors.lastname: Ramsden
authors.forename: A W
authors.initials: AW
authors.lastname: Boylston
authors.forename: P J
authors.initials: PJ
authors.lastname: Guillou
mesh_terms: D015870:Gene Expression; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D006684:HLA-DR Antigens; D012333:RNA, Messenger; D016753:Interleukin-10