Alcohol consumption is associated with alterations in macrophage responses to interferon-γ and infection by Salmonella typhimurium

Abuse of ethanol (EtOH) by human beings and administration of EtOH to experimental animals has been shown to be associated with a suppression of the immune system. Consumption of EtOH has also been associated with an increased incidence and severity of infections of human beings and experimental animals, which has been attributed to the immunosuppression associated with EtOH consumption. It has been shown that EtOH also affects the function of macrophages (MO), which are important effector cells in the innate and adaptive immune responses to infectious agents. The present studies were designed to investigate the effects of EtOH on MO function with an animal model of EtOH consumption. The experiments reported in this paper were done with inflammatory MO and were designed to determine the effects of EtOH on the ability of inflammatory MO to respond to interferon-gamma (IFN-gamma) to control the intracellular growth of Salmonella typhimurium, as well as the production of proinflammatory cytokines and nitric oxide. The ability of MO from EtOH-fed mice to respond to bacterial endotoxin (lipopolysaccharide (LPS)) and IFN-gamma was also evaluated. MO isolated from EtOH-fed mice did not respond as well to IFN-gamma as MO isolated from control mice as measured by control of S. typhimurium, as well as tumor necrosis factor (TNF) and nitric oxide production. Interleukin (IL)-6 production was not affected. Activation of MO from EtOH-fed mice with LPS and IFN-gamma produced levels of nitric oxide and TNF only slightly less than the levels seen in MO from control mice, but a significant decrease in IL-6 was seen when MO from EtOH-fed mice were stimulated with this combination. Flow cytometric analyses showed that IFN-gamma receptor expression was not affected by EtOH. Together the data presented in this paper show that consumption of EtOH is associated with changes in inflammatory MO responses to IFN-gamma. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.