The Problem: Alcoholism is an urgent worldwide clinical problem. Pulmonary infections are a major cause of morbidity and mortality in these patients. Alcohol is known to cause abnormalities in pulmonary host defense mechanisms. The pulmonary alveolar macrophage is the primary, resident defense cell in the lung and one of its critical functions is to release chemotaxins for neutrophils. A lack of an appropriate influx of neutrophils may precipitate or perpetuate pulmonary infections. Hypothesis: We hypothesize that alcohol inhibits alveolar macrophage function specifically its ability to release chemotaxins for neutrophils when stimulated.
Our specific aims are to evaluate if alcohol inhibits the release of alveolar macrophage derived chemotaxins for neutrophils in vivo or in vitro and to evaluate the mechanisms whereby alcohol inhibits the release of alveolar macrophage derived chemotaxins for neutrophils. We will evaluate three pathogenic stimuli, staphylococcus aureus, soluble immune complexes and phorbol myristate acetate which cause neutrophil accumulation in the pulmonary parenchyma. Bronchoalveolar lavage from alcohol treated rats and supernate of alveolar macrophages treated with alcohol will be tested for the presence of chemotaxins for neutrophils. Significance: These experiments will define the role of alcohol in causing alveolar macrophage dysfunction. Since alcohol abuse is common in patients who are HIV positive or have AIDS, alcohol may function as a co-factor in precipitating pulmonary infections in these patients. Definition of the role of alcohol may help in the clinical management of patients with AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA008285-03
Application #
2044407
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1989-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202