Ethanol Ingestion Increases Susceptibility of Mice to Listeria monocytogenes

Abstract

Excessive consumption of alcohol is associated with an increase in the frequency and severity of infectious diseases. Ethanol adversely affects specific and nonspecific aspects of the immune response. We used a murine model to determine whether ethanol ingestion impairs host mechanisms of resistance to Listeria monocytogenes. Naive mice and mice immune to L. monocytogenes were pair-fed either a Leiber-DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet for 7 days. Then, nonimmune mice were given a sublethal dose of L. monocytogenes and studied 2 and 5 days after infection, and immune mice were challenged with a lethal dose of L. monocytogenes and studied 5 days after infection. Multifocal liver abscesses developed in nonimmune ethanol-treated and control mice 2 days after infection. Bacterial colony counts in the spleens were similar between the two groups; however, counts in the livers were slightly higher in ethanol-treated mice as compared with those in control mice. Five days after infection the nonimmune ethanol-treated mice had large necrotizing liver granulomas and organ bacterial colony counts 100 to 1000 times higher than those in control mice. Immune ethanol-treated mice had large areas of liver necrosis and inflammation containing numerous Gram-positive bacilli, whereas immune control mice had small, well-formed granulomas and much less necrosis. Organ bacterial colony counts were about 100 times higher in immune ethanol-treated mice as compared with those in immune control mice. Liver enzyme levels and mortality were significantly higher in ethanol-treated immune and nonimmune mice as compared with those in immune and nonimmune control mice. Data support the suggestion that ethanol consumption impairs the development and expression of T cell-mediated immunity of mice to L. monocytogenes, resulting in increased susceptibility to infection with this organism.

Impaired Bactericidal Activity and Host Resistance toListeria monocytogenesandBorrelia burgdorferiin Rats Administered an Acute Oral Regimen of Ethanol

“…It has been important, therefore, to develop suitable animal models in order to provide key insights into the extent to which the detrimental effects on resistance mechanisms are caused only by ethanol. For example, an alcohol-related decrease of protection has been reported to occur in response to viral infection (4) and to listerial infection in mice (24) and during salmonellosis in mice (25). Consistent with these findings are earlier reports of members of our group 1996) showing that after rats were fed intoxicating amounts of ethanol, they developed significant hematologic and immunologic changes, including decreased humoral and cellular immune responses to bacterial antigens.…”

“…Listeriosis is not as severe a disease in rats as it is in mice. The 50% lethal dose (LD 50 ) in mice (13,24) is about a thousandfold less than the amount of Listeria (5 ϫ 10 7 CFU) that was used here to infect our rats, yet all of our test rats survived, including a few that were observed for an additional 2 to 3 weeks after challenge. This would seem to suggest that we might be using an avirulent strain of Listeria.…”

Acute Alcohol Exposure Exerts Anti-Inflammatory Effects by Inhibiting IκB Kinase Activity and p65 Phosphorylation in Human Monocytes

“…The mechanisms of the immunosuppressive effects of acute alcohol use have been linked to alterations in NF-B activation (1)(2)(3). Previous data suggested that universal inhibition of NF-B binding by alcohol via various receptor systems occurs independent of IB␣ degradation (24).…”

“…The complexes are held in the cytoplasm and prevented from activation by a class of proteins referred to as inhibitors of NF-B or IB proteins. Upon stimulation, the IB proteins are phosphorylated by the IB kinases (IKK) 3 IKK␣, IKK␤, and IKK␥, ubiquitinated, and degraded thereby releasing the NF-B complex for nuclear translocation (11). Recent studies have shown that in addition to this canonical NF-B activation, NF-B proteins are modified posttranslationally, and these changes can influence transcriptional activity.…”

“…A cute alcohol consumption is associated with immunosuppressive effects due to impairment in inflammatory mediator production and alterations in innate immune responses resulting in increased susceptibility to infections (1)(2)(3). Acute alcohol exposure decreases production of inflammatory cytokines such as TNF-␣, IL-1␤, and IL-6 both in vivo and in vitro in human and murine monocytic cells (4 -6).…”