title: Anti-interleukin-6 antibody treatment restores cell-mediated immune function in mice with acute ethanol exposure before burn trauma.
abstract: BACKGROUND
  Previous studies from this laboratory reported that suppression of cell-mediated immune function was coincident with elevated interleukin (IL)-6 production after acute ethanol exposure before burn trauma, compared with either insult alone. The goal of this study was to investigate whether treatment with an anti-IL-6 antibody could restore immunocompetence in mice subjected to burn trauma with previous exposure to alcohol, as assessed by delayed-type hypersensitivity (DTH) and mitogen-induced splenocyte proliferative responses.
  
  
  METHODS
  Mice given an ethanol treatment designed to reach a blood alcohol level of 100 mg/dl before a 15% total body surface area burn injury were treated with an anti-IL-6 antibody at 30 min and 24 hr postinjury.
  
  
  RESULTS
  Burn/ethanol mice exhibited a 91% suppression of the DTH response ( < 0.01) and a 76% suppression of mitogen-induced splenocyte proliferation (p < 0.01) at 48 hr postinjury, along with increased levels of circulating and splenic macrophage-derived IL-6, compared with all other treatment groups. After anti-IL-6 antibody administration to burn/ethanol mice, there was a 25% (p < 0.05) and 63% (p < 0.01) recovery of the DTH and splenocyte proliferative responses, respectively. Addition of exogenous IL-6 to splenocyte cultures isolated from anti-IL-6 antibody-treated burn/ethanol mice resulted in a 70% inhibition of mitogen-induced proliferative responses (p < 0.03).
  
  
  CONCLUSIONS
  These data confirm previous findings that burn in combination with acute ethanol exposure suppresses cell-mediated immune function compared with either insult alone. Furthermore, the ability of the anti-IL-6 antibody treatment to improve cellular immune responses in the burn/ethanol group suggests that blocking this cytokine may be beneficial for the ethanol-exposed, thermally injured individual.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Fontanilla
authors.forename: D E
authors.initials: DE
authors.lastname: Faunce
authors.forename: M S
authors.initials: MS
authors.lastname: Gregory
authors.forename: K A
authors.initials: KA
authors.lastname: Messingham
authors.forename: E A
authors.initials: EA
authors.lastname: Durbin
authors.forename: L A
authors.initials: LA
authors.lastname: Duffner
authors.forename: E J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D002056:Burns / Q000188:drug therapy / Q000276:immunology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000906:Antibodies; D002492:Central Nervous System Depressants; D000431:Ethanol; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors