Association of chronic alcohol consumption and increased susceptibility to and pathogenic effects of pulmonary infection with respiratory syncytial virus in mice

Abstract

Chronic alcohol abuse by human beings has been shown to be associated with increased susceptibility to pulmonary infections and severity of inflammatory responses associated with pulmonary infection. On the basis of the higher likelihood of exposure to respiratory viruses, people who abuse alcohol would logically be susceptible to respiratory viral infections. To test this hypothesis, mice were provided alcohol in drinking water for 13-16 weeks with the Meadows-Cook protocol and infected intranasally with respiratory syncytial virus. At various times after infection, severity of infection was determined by evaluation of cellular and cytokine composition of bronchoalveolar lavage fluid (BALF) and histologic evaluation of inflammation. Infection was associated with neutrophil infiltration in both groups, but the proportion and number of neutrophils in BALF were significantly greater in the alcohol consumption group than in the control group. Concentrations of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 in BALF in the alcohol consumption group were increased. Interferon (IFN)-gamma concentrations were lower in the alcohol consumption group at later times of infection. Pulmonary inflammation was cleared by 3-5 days after infection in the control group. In contrast, pulmonary inflammation was evident in the alcohol consumption group after 7 days of infection, and some mice showed severe inflammation with hemorrhage and edema. IFN-alpha/beta was evident in BALF at low concentrations in the alcohol consumption group for several days after infection, and increased mRNA for IFN-alpha/beta was also evident in the alcohol consumption group. This was accompanied by the presence of virus in this group at these times of infection. Chronic alcohol consumption increased severity of pulmonary infection with a virus that naturally infects hosts by an aerosol route. Infection of mice that had consumed alcohol chronically was more severe in terms of increased proinflammatory cytokine production, inflammation, and a failure to clear the virus from the lungs.

Alcohol, Signaling, and ECM Turnover

“…In mouse models of tuberculosis, excessive alcohol feeding impaired pathogen clearance, blunted CD4+ and CD+ T lymphocyte responses, decreased lymphocyte proliferation, and IFN-c levels in CD4+ T (Mason et al, 2004). Similarly, decreased ability to clear respiratory syncytial virus (RSV) infection despite increased IFN-a and IFN-b induction, progressive loss of CD+ T cells, increased injury and lethality along with increased inflammation reported in animal models of chronic alcohol feeding (Jerrells et al, 2007).…”

“…These observations have since then been confirmed by epidemiological and laboratory studies (MacGregor et al, 1978;Mason et al, 2004;Saitz et al, 1997;Schmidt and De Lint, 1972;Zaridze et al, 2009). More recently, alcohol abuse has also been associated with increased incidence and severity of acute respiratory distress syndrome (ARDS) (Esper et al, 2006;Moss et al, 1996), increased risk for viral and fungal infections and, subsequent susceptibility to secondary bacterial infections (Fong et al, 1994;Jerrells et al, 2007). The increased susceptibility of alcohol abusers to a variety of lung infections is attributed largely to alcohol-mediated alterations in innate and adaptive immunity (Happel and Nelson, 2005;Joshi and Guidot, 2007;Szabo and Mandrekar, 2009).…”

Response to Comment on “Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections”

“…It is also important to examine other immune responses, especially Ab production, which appears as early as day 7; they are critical for control of influenza as published recently (10). Indeed, other studies showed that ethanol can inhibit TNF (11,12), NK cells (13), and IFN␥ (14). It also decreases IL-12 and increases IL-10 to cause immune suppression (15).…”

Alcohol-Use Disorders in the Critically Ill Patient

“…27,29 In patients with AUDs, pneumonia is the most common cause of sepsis, 27 as AUDs may increase the risk of both bacterial and viral pneumonia, and patients with AUDs who have viral pneu monia may have an increased risk of bacterial superinfection. [51][52][53] The severity of illness also is heightened in patients with sepsis and AUDs, increasing the need for mechanical ventilation. 27 Severe sepsis in patients with AUDs results in a twofold higher risk of requiring mechanical ventilation and a two-to fourfold higher risk of developing ARDS.…”