Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6.
Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn + ethanol mice was examined. At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn + ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn + ethanol-treated mice. Furthermore, the immune dysfunction observed in burn + ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6.
Faunce
D E
DE
Department of Cell Biology, Neurobiology, and Anatomy, The Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois, USA.
Gregory
M S
MS
Kovacs
E J
EJ
D000818:Animals; D002056:Burns / Q000097:blood / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D015850:Interleukin-6; D000431:Ethanol; D003345:Corticosterone