| Autor: |
J K, Kolls, D, Lei, D, Stoltz, P, Zhang, P O, Schwarzenberger, P, Ye, G, Bagby, W R, Summer, J E, Shellito, S, Nelson |
| Rok vydání: |
1998 |
| Předmět: |
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| Zdroj: |
Alcoholism, clinical and experimental research. 22(1) |
| ISSN: |
0145-6008 |
| Popis: |
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-alpha). This defect can be reversed by priming macrophages with interferon-gamma (IFN-gamma). 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-gamma gene. This strategy resulted in prolonged expression of IFN-gamma in vivo. Moreover, in a model of acute ethanol intoxication, this vector significantly enhanced lipopolysaccharide-induced TNF-alpha responses and lung polymorphonuclear leukocyte recruitment. Furthermore, pulmonary host defenses against Klebsiella pneumoniae were significantly augmented. These enhanced host defenses were not reversed with pretreatment with a polyclonal anti-TNF-alpha antibody, suggesting that IFN-gamma's effect was through a non-TNF-alpha-dependent mechanism. These data demonstrate that ethanol-induced suppression of pulmonary host defenses can be reversed with IFN-gamma gene therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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