Smoking and Ethanol-Induced Defects in Pneumonia Defense
Principal Investigator: Martha J Gentry-Nielsen
Abstract: The goal of this application is to use a novel rat model to study the compounding effects of cigarette smoke and alcohol abuse on susceptibility to severe pneumococcal pneumonia. Pneumonia is a major cause of morbidity and mortality in alcoholics, and the pneumococcus is the most common bacterial cause. Alcoholics have a higher incidence of pneumococcal pneumonia and they have a greater likelihood of developing bacteremia, which increases their mortality rate. Although scientists have studied the deleterious effects of ethanol ingestion on resistance to infectious diseases for years, the concurrent effects of smoking have been ignored. Because 80-90% of alcoholics smoke and >50% of multi-pack/day smokers are alcohol dependent, it is imperative to consider the additional effects of smoking when studying alcohol-induced defects in host defense against respiratory infections. Our hypothesis is that smoking exacerbates the detrimental effects of ethanol ingestion on host defense mechanisms critical for protection against lethal pneumococcal pneumonia. To test this hypothesis, rats will be exposed twice daily to cigarette smoke or room air in whole body chambers. Half of the rats also will be fed ethanol in a liquid diet. In Specific Aim 1, the rats will be infected intranasally, and the numbers of pneumococci reaching their lungs will be quantified by plate-counts. Movement of the organisms into the lungs will be correlated with alterations in the ciliary beat frequency of the rats' tracheal epithelial cells. In Specific Aim 2, novel in vitro assays will be used to determine the effects of ethanol ingestion, with and without smoke exposure, on the ability of the rats' pulmonary neutrophils to phagocytose and kill pneumococci. In Specific Aim 3, quantitative blood cultures will be used to determine the separate and combined effects of smoke exposure and ethanol ingestion on bacteremia development after establishment of pneumonia. Bacteremia will be correlated with mortality for 10-days post-infection with the use of a hypothermia model to predict death and determine the appropriate time for euthanasia.
Funding Period: 2001-12-01 - 2006-11-30
more information: NIH RePORT
- Smoke exposure exacerbates an ethanol-induced defect in mucociliary clearance of Streptococcus pneumoniaeElizabeth A Vander Top
Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA
Alcohol Clin Exp Res 29:882-7. 2005..Both cigarette smoke and ethanol (EtOH) exposure alter ciliary beating and protein kinase activity in the respiratory mucosa in vitro, but their effects on bacterial clearance in the intact animal have not been determined...
- Smoke exposure and ethanol ingestion modulate intrapulmonary polymorphonuclear leukocyte killing, but not recruitment or phagocytosisElizabeth A Vander Top
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA
Alcohol Clin Exp Res 30:1599-607. 2006..The primary cellular defense against pneumococci within the lungs is the polymorphonuclear leukocyte (PMN). Cigarette smoke and ethanol (EtOH) are known to alter certain PMN functions, but little is known about their concurrent effects...