22 research outputs found
The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy
Effects of gestational thiamine-deprivation and/or exposure to ethanol on crucial offspring rat brain enzyme activities
Central mineralocorticoid receptor blockade decreases plasma TNF-α after coronary artery ligation in rats
Direct demonstration of increases in cytosolic free Ca2+ during stimulation of pancreatic enzyme secretion
Acute Ethanol Exposure Attenuates Pattern Recognition Receptor Activated Macrophage Functions
Both clinical and experimental data have linked acute ethanol exposure to increased susceptibility to infection as well as increased morbidity and mortality after injury. Macrophages play an integral role in the innate immune system and are important in priming the adaptive immune system. In this study, we investigated the effect of a single in vivo exposure of macrophages to physiologically relevant levels of ethanol (1.2 and 2.9 g/kg) followed by ex vivo stimulation with lipopolysaccharide (LPS) or bacteria. Our study confirms the work of others showing that a single administration of ethanol suppresses the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-12 in response to LPS. There was no effect of ethanol on LPS induction of cytokine production at 30 min after treatment. In contrast, at 3 h, both doses of ethanol exposure decreased ex vivo TNF-α production by splenic and alveolar macrophages. Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNF-α production at 3 and 6 h after ethanol administration, as well as decreased IL-6 and IL-12 production after 6 h, as compared to control (saline-treated groups). Alveolar macrophages behaved similarly at 3 h after ethanol treatment. LPS-stimulated production of TNF-α and IL-6 was reduced at 3 h after ethanol administration, when compared with the saline-treated animals. Alveolar macrophages stimulated for 3 h with bacteria also showed decreased TNF-α and IL-6 production after harvested from mice given 2.9 g/kg ethanol for 3 h. This time point and high dose of ethanol also resulted in decreased Pseudomonas aeruginosa phagocytosis by alveolar macrophages. Taken together, we conclude that the effects of physiological levels of ethanol are dose dependent, have effects that last after ethanol is cleared from the circulation, and can affect multiple macrophage functions