Discrepancy in the abilities of lymphokines and bacteria to mediate tumor protection in vivo and/or tumoricidal activity by macrophages in vitro.
In the present study, the ability of lymphokines (MAF and IFN gamma) and microbial agents (CP and LM) to induce and maintain tumoricidal activity in BMMP in vitro and to enhance local resistance to the DA rat D-12 ascites tumor in vivo was assessed comparatively. Under standard conditions in vitro, i.e., when present during the 24-hr induction and the 36-hr effector phase, both lymphokines and microbes were similarly potent for eliciting tumoricidal activity in BMMP. When the activating agents were present only during the induction phase, and effector cells were interacted with tumor targets after a 24-hr interval, clear differences were observed: BMMP which had been incubated with lymphokines had largely if not completely lost their tumoricidal activity; in contrast, BMMP which had been incubated with microbes still manifested considerable tumoricidal activity. Experiments performed to assess the in vivo significance of the discrepancy established in vitro have shown that resistance to the D-12 ascites tumor was markedly enhanced after local inoculation of microbes but was affected very little or not at all by soluble lymphokines. The causes responsible for the discrepancy in the antitumor potential of lymphokines vs. microbes are probably manifold. Extensive attempts to improve the efficacy of lymphokines by repeated administration or by incorporation into liposomes were not successful.
Keller
R
R
Immunobiology Research Group, Institute for Immunology and Virology, University of Zurich, Switzerland.
Keist
R
R
Schwendener
R A
RA
D000818:Animals; D003602:Cytotoxicity, Immunologic; D008081:Liposomes; D008089:Listeria monocytogenes / Q000276:immunology*; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009374:Neoplasms, Experimental / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D008081:Liposomes; D008222:Lymphokines