N-acetylcysteine improves group B streptococcus clearance in a rat model of chronic ethanol ingestion.

BACKGROUND: Sepsis is the most common risk factor associated with acute respiratory distress syndrome (ARDS) and results in a 40-60% mortality rate due to respiratory failure. Furthermore, recent epidemiological studies have demonstrated that a history of alcohol abuse increases the risk of ARDS by 3.6-fold. More recently, group B streptococcus (GBS) infections in nonpregnant adults have been increasing, particularly in alcoholics where there is an increased risk of lobular invasion and mortality. We have shown in an established rat model that chronic ethanol ingestion impaired macrophage internalization of inactivated infectious particles in vitro and enhanced bidirectional protein flux across the alveolar epithelial-endothelial barriers, both of which were attenuated when glutathione precursors were added to the diet. We hypothesized that chronic ethanol ingestion would increase the risk of infection even though GBS is less pathogenic but that dietary N-acetylcysteine (NAC), a glutathione precursor, would improve in vivo clearance of infectious particles and reduce systemic infection. METHODS: After 6 weeks of ethanol feeding, rats were given GBS intratracheally and sacrificed 24 hours later. GBS colony-forming units were counted in the lung, liver, spleen, and bronchoalveolar lavage fluid. Acute lung injury in response to GBS was also assessed. RESULTS: Chronic ethanol exposure decreased GBS clearance from the lung indicating an active lung infection. In addition, increased colonies formed within the liver and spleen indicated that ethanol increased the risk of systemic infection. Ethanol also exacerbated the acute lung injury induced by GBS. NAC supplementation normalized GBS clearance by the lung, prevented the appearance of GBS systemically, and attenuated acute lung injury. CONCLUSIONS: These data suggested that chronic alcohol ingestion increased the susceptibility of the lung to bacterial infections from GBS as well as systemic infections. Furthermore, dietary NAC improved in vivo clearance of GBS particles, attenuated acute lung injury, and disseminated infection.

In utero ethanol exposure impairs defenses against experimental group B streptococcus in the term Guinea pig lung.

BACKGROUND: The effects of fetal alcohol exposure on the risks of neonatal lung injury and infection remain under investigation. The resident alveolar macrophage (AM) is the first line of immune defense against pulmonary infections. In utero ethanol (ETOH) exposure deranges the function of both premature and term guinea pig AM. We hypothesized that fetal ETOH exposure would increase the risk of pulmonary infection in vivo. METHODS: We developed a novel in vivo model of group B Streptococcus (GBS) pneumonia using our established guinea pig model of fetal ETOH exposure. Timed-pregnant guinea pigs were pair fed +/-ETOH and some were supplemented with the glutathione (GSH) precursor S-adenosyl-methionine (SAM-e). Term pups were given GBS intratracheally while some were pretreated with inhaled GSH prior to the experimental GBS. Neonatal lung and whole blood were evaluated for GBS while isolated AM were evaluated using fluorescent microscopy for GBS phagocytosis. RESULTS: Ethanol-exposed pups demonstrated increased lung infection and sepsis while AM phagocytosis of GBS was deficient compared with control. When SAM-e was added to the maternal diet containing ETOH, neonatal lung and systemic infection from GBS was attenuated and AM phagocytosis was improved. Inhaled GSH therapy prior to GBS similarly protected the ETOH-exposed pup from lung and systemic infection. CONCLUSIONS: In utero ETOH exposure impaired the neonatal lung's defense against experimental GBS, while maintaining GSH availability protected the ETOH-exposed lung. This study suggested that fetal alcohol exposure deranges the neonatal lung's defense against bacterial infection, and support further investigations into the potential therapeutic role for exogenous GSH to augment neonatal AM function.

Transport properties of the mesothelium and interstitium measured in rabbit pericardium.

The contribution of the pleural mesothelium to pleural liquid and protein transport is still vigorously debated. Recent in vitro studies of stripped pleural membrane and free-standing pericardium have demonstrated active ion solute coupled transport of liquid and transcytosis of protein. However, the relative contribution of the passive transport properties of the pleural mesothelium compared to the pleural interstitium has not been extensively studied. In in vitro studies, we measured the albumin diffusion coefficient, reflection coefficient, hydraulic conductivity and electrical resistance of rabbit pericardium. We used two techniques, treatment with 40 muM nocodazole and a 1-min hypotonic cell lysis with distilled water, to eliminate the effect of the two mesothelial layers on diffusional and hydraulic resistances. Each technique increased the albumin diffusion coefficient and hydraulic conductivity 3- to 4-fold. In hydraulic conductivity experiments using tracer 125I-albumin, nocodazole reduced the reflection coefficient to zero, rendering the pericardium completely permeable to albumin. We applied the cell-lysis technique to the pleural and pericardial mesothelium in sequence to evaluate the separate contribution of each mesothelium. Both diffusional and hydraulic resistances, but not electrical resistance, of the mesothelium were overestimated by the cell-lysis technique. The pleural mesothelium contributed at most 30% of diffusional resistance, 10% of hydraulic resistance and 14% of electrical resistance of the total pericardial resistances. We conclude that the pleural mesothelium is not the primary barrier to protein diffusion or bulk flow of liquid from the pericardial microcirculation to the pleural liquid.