Anti-interleukin-6 antibody treatment restores cell-mediated immune function in mice with acute ethanol exposure before burn trauma

Alcohol Clin Exp Res. 2000 Sep;24(9):1392-9.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Antibodies / therapeutic use
  • Burns / drug therapy
  • Burns / immunology*
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Hypersensitivity, Delayed / drug therapy
  • Hypersensitivity, Delayed / immunology*
  • Immune Tolerance
  • Immunity, Cellular / immunology*
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / drug effects

Substances

  • Antibodies
  • Central Nervous System Depressants
  • Interleukin-6
  • Ethanol