Alcoholism, clinical and experimental research
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Alcohol. Clin. Exp. Res. · Jul 2005
Temporal differences in the ability of ethanol to modulate endotoxin-induced increases in inflammatory cytokines in muscle under in vivo conditions.
Acute alcohol (EtOH) intoxication may both antagonize and potentiate the ability of monocytes/macrophages to respond to endotoxin (lipopolysaccharide [LPS]). The suppressive effects of EtOH predominate when the duration between EtOH and LPS administration is relatively short, whereas sensitization is observed under conditions when there is a relatively longer delay between EtOH and LPS exposure. Striated muscle is now recognized to possess components of both the afferent and efferent limbs of the innate immune system. The aim of the present study was to determine whether the interval between EtOH and LPS administration differentially affects the mRNA content for selected elements of the innate immune response in skeletal and cardiac muscle and to compare such changes with those occurring in liver and spleen. ⋯ Under in vivo conditions, the interval between EtOH exposure and LPS differentially affected the synthesis of various cytokines. In this regard, EtOH administered within two hr of LPS generally suppressed IL-6, IL-1beta, and TNF-alpha mRNAs in muscle, heart, liver, and spleen. Delaying the exposure of animals to LPS for 24 hr after EtOH, however, accentuated the increase in IL-6 and HMGB1, and for IL-6, this increased sensitivity appeared localized to striated muscle.