ACTIVATION OF ALVEOLAR MACROPHAGES AND LUNG HOST DEFENSES USING TRANSFER OF THE INTERFERON-GAMMA GENE

Interferon-gamma (IFN-gamma) is a critical cytokine in pulmonary host defenses against both intracellular and extracellular pathogens. To in vestigate whether this cytokine could be used therapeutically, we cons tructed an E1-deleted recombinant adenovirus encoding murine IFN-gamma . After intratracheal inoculation in rats, this vector resulted in pro longed expression of functional cytokine in vivo, as demonstrated by i ncreased alveolar macrophage class II major histocompatibility complex expression, enhanced release of tumor necrosis factor in response to lipopolysaccharide, and enhanced host defenses against Pseudomonas aer uginosa. We postulate that this vector may be useful to study the role of exogenous IFN-gamma in a variety of pulmonary intracellular and ex tracellular pathogens.