Interleukin-4 treatment restores cellular immunity after ethanol exposure and burn injury.
BACKGROUND
Previous studies from this laboratory showed that the suppression of cell-mediated immunity after the combined injury of ethanol exposure and burn is mediated by increased presence of the proinflammatory cytokine interleukin (IL)-6. IL-4 is a T-helper cell type 2 lymphocyte-derived cytokine that serves to down-regulate the inflammatory response. Therefore, the goal of this study was to evaluate the effects of ethanol exposure and burn injury on lymphocyte production of IL-4 and to determine whether administration of IL-4 could improve cellular immunity after ethanol exposure and burn injury through modulation of IL-6 levels.


METHODS
Mice were subjected to a 15% total body-surface area burn (or sham) injury 30 min after being given a single dose of alcohol (or saline) designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after burn, mice were treated with IL-4 (or vehicle) and were killed 24 hr later.


RESULTS
Lymphocytes from ethanol/burn mice secreted significantly less IL-4 in comparison to all other groups of mice (p < 0.05). Administration of IL-4 resulted in a complete restoration of the delayed-type hypersensitivity (p < 0.01) and splenocyte proliferative responses (p < 0.05) and a significant reduction in circulating and splenic macrophage-derived IL-6 (p < 0.05). Addition of IL-4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle mice resulted in a complete restoration of splenocyte proliferation and a concomitant attenuation of macrophage IL-6 production.


CONCLUSIONS
These studies suggest that the loss of lymphocyte production of IL-4 after ethanol exposure and burn injury may contribute to the exaggerated production of IL-6, a known mediator of immune suppression after injury. Moreover, the administration of IL-4 may be beneficial for patients with injuries that are characterized by a dysregulated inflammatory response.
Messingham
Kelly A N
KA
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois, USA.
Heinrich
Scott A
SA
Schilling
Eric M
EM
Kovacs
Elizabeth J
EJ
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002056:Burns / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D002492:Central Nervous System Depressants; D015850:Interleukin-6; D015847:Interleukin-4; D000431:Ethanol