title: Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection.
abstract: OBJECTIVE
  The purpose of this study was to compare the production of interleukin-10 (IL-10) by peripheral blood mononuclear cells (PBMC) from injured patients and control subjects to determine the responsible cell types and to relate IL-10 production to the occurrence of sepsis. A mouse model of burn injury was used to confirm the human findings and to assess the importance of IL-10 in the lowered resistance to infection after injury.
  
  
  BACKGROUND
  Severe injury is associated with depressed immune responses. Although IL-10 is known to inhibit several aspects of immune reactivity, the role of IL-10 in postinjury immune suppression remains controversial.
  
  
  METHODS
  Peripheral blood mononuclear cells from 14 burn and 12 trauma patients and 16 healthy individuals were studied at serial intervals for IL-10 production stimulated by a T-cell mitogen, phytohemagglutinin, and by bacterial lipopolysaccharide. To determine the source of IL-10, CD4+ and CD8+ lymphocyte subsets were obtained by selective depletion of PBMC with antibody-coated magnetic beads and were stimulated by anti-CD3 antibody to induce IL-10 secretion. In addition, IL-10 production by patients' PBMC in the first 10 days after injury was assessed for correlation with subsequent septic events. Anti-CD3-stimulated IL-10 production also was determined for CD4- and CD8-enriched lymphocyte subsets obtained by antibody and complement depletion of splenocytes harvested from groups of burn and sham burn mice at day 10 after injury, the time of maximal susceptibility to a septic challenge, cecal ligation and puncture (CLP). Finally, to test the importance of IL-10 in immune suppression in vivo, groups of burn and sham burn mice were treated with anti-IL-10 monoclonal antibody or control immunoglobulin G (IgG) on days 1 and 3 postinjury and were observed for survival after CLP on day 10.
  
  
  RESULTS
  Patients' PBMC produced significantly more IL-10 than did controls' PBMC 7 to 14 days after injury. Patients' CD4+ (T-helper) but not CD8+ (T-cytotoxic) lymphocytes also showed increased IL-10 production versus those of control subjects early after injury. Increased PBMC IL-10 production in the first 10 days postinjury correlated significantly (p < 0.05) with subsequent septic events. Burn mouse CD4-enriched but not CD8-enriched splenocytes produced more IL-10 than did sham burn splenocyte subsets on day 10 after injury. Burn mice treated with anti-IL-10 antibody but not with control IgG had significantly increased survival after CLP.
  
  
  CONCLUSIONS
  Serious injury in humans and in a mouse burn model is followed by increased stimulated production of IL-10 by cells of the immune system. The CD4+ T-helper cells appear to be a major source of IL-10 after injury. In injured patients, increased IL-10 production is correlated with subsequent septic events, and in the burn mouse, IL-10 appears to induce decreased resistance to infection.
authors.affiliation: Department of Surgery, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lyons
authors.forename: J L
authors.initials: JL
authors.lastname: Kelly
authors.forename: M L
authors.initials: ML
authors.lastname: Rodrick
authors.forename: J A
authors.initials: JA
authors.lastname: Mannick
authors.forename: J A
authors.initials: JA
authors.lastname: Lederer
mesh_terms: D000328:Adult; D000818:Animals; D002056:Burns / Q000276:immunology; D002432:Cecum; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007239:Infections / Q000276:immunology*; D015601:Injury Severity Score; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008026:Ligation; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D008875:Middle Aged; D010835:Phytohemagglutinins; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D007371:Interferon-gamma