title: Protective effects of early interleukin 10 antagonism on injury-induced immune dysfunction.
abstract: OBJECTIVE
  Interleukin 10 (IL-10) plays a central role in the development of postinjury immune suppression, and early in vivo IL-10 antagonism can be protective.
  
  
  METHODS
  Male A/J mice underwent sham or burn injury and were treated with monoclonal anti-IL-10 antibody or control antibody at 1 day or 3 days after injury. Their ability to survive polymicrobial sepsis induced by the cecum ligation and puncture (CLP) technique was then tested. The response of sham- and burn-injured mice and burn-injured mice treated with anti-IL-10 to immunization with a T-cell-dependent antigen, trinitrophenyl (TNP)-haptenated ovalbumin (TNP-OVA) was also assessed.
  
  
  METHODS
  Mortality was monitored for a total of 7 days after CLP to assess the effect of anti-IL-10 therapy on the survival of burn-injured, immunecompromised mice. Serum antibody isotype formation was measured in sham- and burn-injured mice and burn-injured mice treated with anti-IL-10 to determine how IL-10 antagonism influenced helper T-cell responses in vivo. In vitro cytokine production by antigen-stimulated spleen cells was assessed to study the effect of blocking IL-10 activity at 1 day vs 3 days after burn injury.
  
  
  RESULTS
  Treating mice with anti-IL-10 at 1 day after injury significantly improved CLP survival, whereas delaying treatment 3 days had no beneficial effect. The analysis of T-cell function in vivo as determined by serum antibody isotype formation indicated that anti-IL-10 treatment at 1 day or 3 days after injury increased T helper cell 1-type antibody formation to sham injury levels by day 10. Moreover, these treatments restored the injury-induced reduction of antigen-stimulated IL-2, interferon gamma, and IL-10 production.
  
  
  CONCLUSIONS
  Interleukin 10 plays an early role in the development of burn injury-induced immune suppression. Its in vivo inhibition at 1 day after injury may be a useful approach toward preventing the development of injury-induced immune dysfunction and may do so by restoring T-cell function and cytokine production.
authors.affiliation: Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lyons
authors.forename: A
authors.initials: A
authors.lastname: Goebel
authors.forename: J A
authors.initials: JA
authors.lastname: Mannick
authors.forename: J A
authors.initials: JA
authors.lastname: Lederer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D002056:Burns / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D007108:Immune Tolerance / Q000187:drug effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000517:prevention & control*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D016753:Interleukin-10