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Background Ethanol ( Et OH) exposure prior to traumatic injury, such as a burn, elevates systemic and local inflammatory responses and increases morbidity and mortality. Adipose is a large tissue mass that is often inflamed during obesity or other stresses, which disturbs metabolic homeostasis. To date, there has been little investigation into the inflammatory response of adipose tissue after combined Et OH exposure and burn injury. Methods Two Et OH exposure regimens were utilized to examine the role of inflammation in adipose tissue after Et OH and burn injury. Mice were either given a single or episodic binge exposure to Et OH or saline followed by scald (burn) or sham injury 30 minutes later. Twenty-four hours post injury, serum and adipose tissue were collected for assessment of inflammatory mediators. Results Single binge Et OH alone induced no inflammation in adipose when compared with sham vehicle-treated mice. However, single binge Et OH followed by burn injury induced significant elevations in m RNA and protein concentrations of pro-inflammatory mediators interleukin-6 ( IL-6), KC, and monocyte chemoattractant protein 1 compared with either insult alone or sham vehicle group. Additionally, Et OH exposure and burn injury significantly blunted inducible nitric oxide synthase (i NOS), indicating a complex inflammatory response. Episodic binge Et OH exposure followed by burn injury exacerbated the postburn adipose inflammatory response. The magnitude of the episodic binge-induced inflammatory parameters postburn were 2- to 5-fold greater than the response detected after a single exposure of Et OH, indicating Et OH-induced potentiation of burn-induced inflammatory response. Finally, inflammatory loci and crown-like structures in adipose were significantly increased by episodic binge Et OH and burn injury. Conclusions This is the first report of binge and burn-induced crown-like structure formation. Evidence presented herein suggests an important role for alcohol and burn as an additional mediator of adipose inflammation in postburn injury, a common complication in burn patients. [ABSTRACT FROM AUTHOR]

Background: Clinical and laboratory evidence suggests that alcohol consumption prior to burn injury leads to dysregulated immune function and subsequent higher rates of morbidity and mortality. Our laboratory previously observed higher levels of pro-inflammatory cytokines and leukocyte infiltration in the lungs of mice following ethanol and burn injury. To understand the mechanism of the increased inflammatory response, we looked at different signaling initiators of inflammation including toll-like receptors 2 and 4 (TLR2 and 4) pathways. Methods: Wild-type, TLR2, and TLR4 knockout mice were treated with vehicle or a single binge dose of ethanol (1.11 g/kg) and subsequently given a sham or burn injury. Twenty-four hours postinjury, systemic and pulmonary levels of pro-inflammatory cytokines were quantified, and differences in neutrophil infiltration were determined by histological examination. Results: Higher numbers of neutrophils were observed in the lungs of wild-type mice following the combined insult of ethanol and burn injury relative to either injury alone. This increase in leukocyte accumulation was absent in the TLR4 knockout mice. Circulating levels of IL-6 and tumor necrosis factor-α were also elevated in wild-type mice but not in TLR4 knockout mice. Consistent with these findings, pulmonary levels of KC and IL-6 were increased in wild-type mice following burn and ethanol compared to burn injury alone as well as to their TLR4 knockout counterparts. In contrast, TLR2 knockout mice displayed similar levels, to wild-type mice, of neutrophil infiltration as well as IL-6 and KC in the lung. Conclusions: These data suggest that TLR4 signaling is a crucial contributory component in the exuberant inflammation after ethanol and burn injury. However, TLR2 does not appear to play a vital role in the aberrant pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Early clearance of a thymidine kinase-deficient strain of herpes simplex virus type 2 from the female genital tract required T-cell-produced gamma interferon (IFN-γ). Transfer of activated CD8+ T cells to irradiated C57BL/6 mice resulted in rapid virus clearance, but clearance was greatly delayed in recipients deficient in the IFN-γ receptor (IFN-γ R). Early virus clearance was demonstrated in radiation chimeras in which IFN-γ R expression was limited to parenchymal cells, but resolution was significantly delayed in chimeras deficient in IFN-γ R expression and chimeras expressing IFN-γ R only on hematopoietic cells. Together, these results suggest that early IFN-γ-mediated protection was manifested mainly by stimulation of genital parenchymal cells. [ABSTRACT FROM AUTHOR]