Journal article
Adenoviral-Mediated Interferon-γ Gene Therapy Augments Pulmonary Host Defense of Ethanol-Treated Rats
Alcoholism, clinical and experimental research, Vol.22(1), pp.157-162
Received for publication May 1, 1997; accepted August 22, 1997
02/1998
DOI: 10.1111/j.1530-0277.1998.tb03632.x
PMID: 9514301
Abstract
Alcohol has long been recognized as an immunosuppressive drug and a risk factor for a spectrum of infectious diseases. Among these infections, bacterial pneumonias are most closely correlated with alcohol abuse. One potential mechanism of ethanol-induced immunosuppression is through its ability to suppress alveolar macrophage production of tumor necrosis factor (TNF-α). This defect can be reversed by priming macrophages with interferon-γ (IFN-γ). We hypothesized that macrophage priming in vivo in a model of acute ethanol intoxication could augment pulmonary host defenses. To test this hypothesis, we used adenoviral-mediated gene transfer of the IFN-γ gene. This strategy resulted in prolonged expression of IFN-γ in vivo. Moreover, in a model of acute ethanol intoxication, this vector significantly enhanced lipopolysaccharide-induced TNF-α responses and lung polymorphonuclear leukocyte recruitment. Furthermore, pulmonary host defenses against Klebsiella pneumoniae were were significantly augmented. These enhanced host defenses were not reversed with pretreatment with a polyclonal anti-TNF-α antibody, suggesting that IFN-γ's effect was through a non-TNF-α-dependent mechanism. These data demonstrate that ethanol-induced suppression of pulmonary host defenses can be reversed with IFN-γ gene therapy.
Details
- Title: Subtitle
- Adenoviral-Mediated Interferon-γ Gene Therapy Augments Pulmonary Host Defense of Ethanol-Treated Rats
- Creators
- Jay K. Kolls - Louisiana State UniversityDinghua Lei - Louisiana State UniversityDavid Stoltz - Louisiana State UniversityPing Zhang - Louisiana State UniversityPaul O. Schwarzenberger - Louisiana State UniversityPeng Ye - Louisiana State UniversityGreg Bagby - Louisiana State UniversityWarren R. Summer - Louisiana State UniversityJudd E. Shellito - Louisiana State UniversitySteve Nelson - Louisiana State University
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.22(1), pp.157-162
- Edition
- Received for publication May 1, 1997; accepted August 22, 1997
- DOI
- 10.1111/j.1530-0277.1998.tb03632.x
- PMID
- 9514301
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Blackwell Publishing Ltd
- Number of pages
- 6
- Language
- English
- Date published
- 02/1998
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984297501602771
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