Augmentation by bacterial lipopolysaccharide of antitumor potency of murine recombinant interferon-gamma against Lewis lung adenocarcinoma.
Stimulation by recombinant murine interferon-gamma (rMuIFN-gamma) of host defenses against the growth of Lewis lung adenocarcinoma, cell line 3LL, in the lung was examined. 3LL cells were resistant to in vitro antiproliferative activities of rMuIFN-gamma. On the other hand, rMuIFN-gamma augmented the killer activities of the non-adherent population of spleen cells and peripheral blood mononuclear cells (PBMC) in vivo, and the IFN also stimulated the cytostatic activities of peritoneal and splenic macrophages, but not alveolar macrophages. The combination of rMuIFN-gamma with LPS synergistically activated macrophages from the lung, as well as the peritoneal cavity and the spleen, to become both cytostatic and cytolytic against 3LL cells. The macrophages activated in vitro by simultaneous incubation with these agents markedly suppressed the growth of 3LL cells in vivo. The growth in the lung of 3LL cells implanted iv was significantly (P less than 0.05) suppressed by combination therapy with rMuIFN-gamma and LPS, but not by either agent alone. These results indicate that the potency of rMuIFN-gamma action against 3LL cells can be augmented by combination with LPS, mainly through synergistic macrophage activation.
Nagao
S
S
Sato
K
K
Ogawa
H
H
Osada
Y
Y
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D004357:Drug Synergism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma