The long-term impaired macrophages functions are already observed early after high-dose ethanol administration

Herein, we described an experimental model of high-dose ethanol (EtOH) administration, able to induce in vitro impairment in macrophage phagocytic capacity, already observed at 24 h after the last EtOH administration. This phenomenon was characterized by enlarged time required for adhesion and internalization events. Parallel studies documented an overall impaired production of interleukin (IL)-6 and nitric oxide (NO) production by peritoneal macrophages in EtOH-treated mice following interferon (IFN)-γ and lipopolysaccharide (LPS) stimuli. Although the impaired IL-6 response could not be restored by any of the experimental conditions tested, the lower NO response to INF-γ and LPS was overturned by simultaneous IFN-γ/LPS stimuli. It was interesting to notice that high-dose EtOH administration drives peritoneal macrophages towards long-term impairment in phagocytosis capacity with slower adhesion time, but with no impact on the time required for internalization. Moreover, 30 days after the last EtOH administration, lower IL-6 response to INF-γ and impaired NO production were still observed in response to IFN-γ/LPS stimuli, with the IL-6 response to IFN-γ being restored by IFN-γ/LPS stimuli. Histological studies showed that high-dose EtOH administration led to long-term in vivo impairment of antigen-clearance following OVA-driven delayed-type-hypersensitivity induction, characterized by the presence of a large amount of unprocessed OVA surrounded by dermal inflammatory infiltrate, suggesting defective activity of antigen-presenting cells. Together, these findings supported our hypothesis that the poor antigen clearance in vivo may be related to the impaired macrophage function in vitro . These observations in the murine experimental model may reflect some of the consequences of EtOH consumption by humans.