In situ activation of mouse macrophages and therapy of spontaneous renal cell cancer metastasis by liposomes containing the lipopeptide CGP 31362
The purpose of these studies was to determine whether the tumoricidal phenotype of human blood monocytes would be affected by different activation signals. Human monocytes obtained by elutriation of buffy coats were cultured in vitro in medium containing LPS, muramyltripeptide phosphatidylethanolamine (MTP-PE), or a lipopeptide analogue of gram-negative bacteria cell wall. These immunomodulators were added to monocytes in the presence or absence of IFN-gamma. Incubation with LPS, lipopeptide, and MTP-PE rendered the monocyte cytotoxic against allogeneic melanoma cells. Monocytes treated with LPS and lipopeptide (in the absence of IFN-gamma) secreted IL 1, TNF, and PGE2. In contrast, monocytes incubated with MTP-PE (in the absence of IFN-gamma) secreted only TNF. When the monocytes were coincubated with IFN-gamma (human but not mouse) and the immunomodulators, IL 1, TNF, and PGE2 were secreted at all test groups. These data show that some immunomodulators can regulate the release of TNF independently of IL 1 and that not all "activated tumoricidal macrophages" share identical phenotypes.