Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Abstract

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. J. Leukoc. Biol. 64: 724-732; 1998.

Injury-Induced Suppression of Effector T Cell Immunity Requires CD1d-Positive APCs and CD1d-Restricted NKT Cells

“…Although fewer in number, studies by our laboratory and others have clearly shown that injury profoundly impacts the reactivity of the adaptive immune system as well (3,8,12,26,27). The importance of having intact adaptive immunity after injury is demonstrated by key observations by laboratories that studied the septic response to injury.…”

“…Eight-to 10-wk-old male BALB/c and BALB/c CD1d knockout (ko) 3 mice used in these studies were obtained from The Jackson Laboratory. NKT cell-deficient BALB/c-J␣281 ko mice were provided by M. Taniguchi (RIKEN, Yokohama, Japan).…”

“…Immune function after major trauma has been well studied and is known to go awry due, in part, to the overproduction of numerous proinflammatory mediators (2)(3)(4)(5), alterations in the production of granulocyte and monocyte progenitors (6,7), and increased production of immunomodulatory cytokines, including IL-4, IL-10, and TGF-␤ (4, 8 -10). Investigations over the past two decades have provided new insight into the roles of macrophages, dendritic cells, and T lymphocytes in regulating immunity during injury and sepsis (11)(12)(13).…”

Regulation of glucocorticoid sensitivity in thymocytes from burn-injured mice

“…Many studies have reported thymic involution caused by a systemic increase of GC during stress (8,35,36). Thermal injury is an extremely stressful event, and the associated response is characterized by a dramatic increase in plasma GC levels, which reach maximal values during the first 48 h postburn injury (11). Several studies have demonstrated a link between GC production following thermal injury and immune dysfunction (3,32).…”

Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK pathway and promotes bacterial translocation after alcohol and burn injury

“…Glucocorticoids are pleiotropic hormones with a wide spectrum of immunomodulatory and anti-inflammatory properties. (3,8,18,21,39,49,50). They function by binding to glucocorticoid receptor, which resides in an inactive form in the cytoplasm of target cells (3,44,49).…”