Alcoholism is a major risk factor for severe bacterial pneumonia. Ethanol has been reported to cause suppression of selected polymorphonuclear leukocyte (PMN) and alveolar macrophage (AM) functions which provide critical components of normal pulmonary antibacterial defenses. The mechanisms of alcohol- induced suppression of host defenses are unknown. We postulate that alcohol produces these effects by inhibiting the production and/or release of tumor necrosis factor (TNF) from AM. TNF is a polypeptide hormone and is produced in greatest quantity by the AM after exposure to lipopolysaccharide (LPS), components from gram-negative bacterial cell walls. The strong association between TNF production and LPS suggests that TNF may play a central role in mobilizing host defenses against pathogenic bacteria. TNF is an inflammatory mediator and activates phagocytes, enhancing their phagocytic and bactericidal capacity. Our preliminary data support the hypothesis that alcohol inhibits TNF activity and thereby suppresses pulmonary antibacterial defenses. The goal of the proposed studies is to characterize the mechanisms by which alcohol administration, both acute and chronic, impair lung host defenses in a rat model in vivo. We hope to achieve this by determining: 1. the effect of acute and chronic alcoholism on pulmonary antibacterial defenses. 2. the role of TNF in host defense. 3. the effect of acute and chronic alcoholism on TNF. 4. the effect of recombinant TNF administration on alcohol- induced suppression of antibacterial defenses. Analysis of these investigations will contribute to our understanding of the known impairments in host defenses that accompany alcohol abuse and may offer innovative approaches to intervention of infections in alcoholics and other compromised hosts.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AA007710-04
Application #
3452759
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112