Alcohol Exacerbates Murine Pulmonary Tuberculosis

Abstract

Alcohol consumption has been described as a risk factor for infection with Mycobacterium tuberculosis, but its contribution to tuberculosis has been difficult to isolate from other adverse socioeconomic factors. Our objective was to evaluate the impact of alcohol consumption on pulmonary infection with M. tuberculosis in a murine model. BALB/c mice were maintained on the Lieber-DeCarli liquid ethanol diet or a liquid control diet and infected intratracheally with low-dose M. tuberculosis H37Rv. Lung organism burdens, lung and lung-associated lymph node CD4 ؉ -and CD8 ؉ -lymphocyte numbers and rates of proliferation, and CD4 ؉ -lymphocyte cytokine production levels were compared between the groups. The alcohol-consuming mice had significantly higher lung organism burdens than the control mice, and the CD4 ؉ -and CD8 ؉ -lymphocyte responses to pulmonary infection with M. tuberculosis were blunted in the alcohol group. Lymphocyte proliferation and production of gamma interferon were decreased in the CD4؉ lymphocytes from the alcohol-consuming mice. Additionally, lung granulomas were significantly smaller in the alcohol-consuming mice. In conclusion, murine alcohol consumption is associated with decreased control of pulmonary infection with M. tuberculosis, which is accompanied by alterations in the region-specific CD4؉ -and CD8 ؉ -lymphocyte responses and defective lung granuloma formation.For many years, the medical literature worldwide has suggested an association between alcohol consumption and active tuberculosis in humans (7,10,16,19,23,24,28,44). Screening alcohol-abusing subjects in an urban setting for tuberculous infection revealed rates of active tuberculosis that were 28-fold greater than those of age-matched residents and rates of positive tuberculin tests that were 1.5-fold greater than those of agematched residents of the same locale (19). In another setting, heavy alcohol consumption conferred a twofold-heightened risk for developing active tuberculosis (10). Additionally, a person with active tuberculosis who routinely frequented a neighborhood bar was found to have infected 41 persons who were frequent clients of the bar, one-third of whom developed active tuberculosis (24). Similar reports of increased prevalence of tuberculosis in alcohol-consuming subjects exist outside of the United States. In London, England, regular alcohol use increased the risk of contracting tuberculosis more than twofold (28), and alcohol abuse was found to be a risk factor in the acquisition of multidrug-resistant tuberculosis in Russia (44).However, the bulk of the evidence of an association between alcohol consumption and tuberculosis is circumstantial, and not all studies consistently demonstrate this association (34, 42). Among homeless persons in San Francisco, despite very high rates of tuberculosis, alcohol abuse was not found to be a significant risk factor (34). Regular consumers of alcohol frequently have confounding lifestyle factors, such as other substance (i.e., illicit drugs or tobacco) abuse, low socioeco...

Alcohol, Signaling, and ECM Turnover

“…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).…”

“…In this same model of infection, the expression of IL-17, a cytokine which serves as a link between innate and adaptive immunity, is shown to be inhibited by chronic alcohol intake . 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).…”

Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

“…Moreover, mice fed up to 20% ethanol for 5 weeks were still considered healthy enough to tolerate experiments (40,41) prior to infection with S. pneumoniae (41) or Mycobacterium tuberculosis (40). Therefore, this ethanol feeding procedure is suitable for experiments evaluating the effects of alcohol.…”

Tuberculous Tenosynovitis of the Wrist Mimicking a Volar Wrist Ganglion Cyst and Carpal Tunnel Syndrome

“…Animal studies of pulmonary TB have shown decreased lung CD4 and CD8 T cells and diminished proliferation in ethanol-fed mice compared with a control group. [12] In another study, ethanol also significantly decreased the granulomatous response. This was possibly caused by impaired interferongamma (IFN-γ) secretion of T cells that were isolated from the lungs and the mediastinal lymph nodes of the alcohol-consuming mice.…”