Premium
Adenoviral‐Mediated Interferon‐γ Gene Therapy Augments Pulmonary Host Defense of Ethanol‐Treated Rats
Author(s) -
Kolls Jay K.,
Lei Dinghua,
Stoltz David,
Zhang Ping,
Schwarzenberger Paul O.,
Ye Peng,
Bagby Greg,
Summer Warren R.,
Shellito Judd E.,
Nelson Steve
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03632.x
Subject(s) - immunology , tumor necrosis factor alpha , in vivo , lipopolysaccharide , immunosuppression , alveolar macrophage , interferon , priming (agriculture) , macrophage , biology , medicine , pharmacology , in vitro , biochemistry , botany , germination , microbiology and biotechnology
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.