Aerosolized gamma-interferon and lipopolysaccharide enhances cytotoxicity of murine pulmonary alveolar macrophages.
In vivo stimulation of pulmonary alveolar macrophages (PAMs) may enhance tumor cell cytotoxicity. A model using aerosolized gamma-interferon (gamma-IFN) and lipopolysaccharide (LPS) was developed to induce enhanced PAM activation in vivo in C57BL/6 mice. Mice received four doses of aerosol (2 doses/day) consisting of gamma-IFN (10(4) microU/mouse) and LPS (100 micrograms/mouse). Other groups received either gamma-IFN alone, LPS alone, or saline (control). Cells were harvested by bronchoalveolar lavage. Macrophage cell count demonstrated an increase in macrophage recruitment in the gamma-IFN and LPS group. PAMs were evaluated for in vitro cytotoxicity against B16-F10 melanoma cells. Treatment groups demonstrated enhanced cytotoxicity over controls, and the combination (gamma-IFN plus LPS) was significantly better in cell killing than either treatment modality alone (p less than or equal to 0.02). Activated PAMs selectively killed tumor cells, but did not kill the 3T3 fibroblast cell line. Peritoneal macrophages from mice treated by inhalational gamma-IFN + LPS were enhanced (indicating a systemic effect), but not to the same extent as PAMs. These studies suggest that inhalation of gamma-IFN + LPS can selectively enhance in vivo cytotoxicity of murine PAMs. This may potentially be applicable to human tumor management.
Eisenberg
B L
BL
Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Taylor
D D
DD
Weese
J L
JL
D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003602:Cytotoxicity, Immunologic; D007167:Immunotherapy; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000556:secondary* / Q000628:therapy; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000336:Aerosols; D008070:Lipopolysaccharides; D007371:Interferon-gamma