Role of mononuclear phagocyte function in endotoxin-induced tumor necrosis.
The temporal susceptibility of tumors to induction of necrosis and regression by endotoxin was investigated further with a focus on the role of the putative mediator, tumor necrosis factor (TNF). Production of this factor was shown earlier to require prior activation of the mononuclear phagocytic system (MPS). Transplants of Meth A sarcoma or MOPC315 plasmacytoma had no consistent effect on parameters of MPS function such as hepatosplenomegaly, carbon clearance and non-specific antibacterial resistance at times that they were sensitive to induction of necrosis. Moreover, TNF, quantified by its necrotizing and regressing activity in vivo, could not be detected in the serum of tumor hosts after a necrotizing dose of endotoxin, while much smaller volumes of serum with TNF (TNS) of appropriately treated donor mice showed activity. As repeated incubation of TNS with Meth A cells at 37 degrees C hardly removed its in vivo activity against Meth A, immediate absorption of produced TNF to the tumor cell mass seems a less likely cause. Cytostatic activity, another property attributed to TNF, was hardly increased in post-endotoxin tumor host serum, while TNS is highly cytostatic. It is concluded that induction of tumor necrosis is not dependent on MPS activation. A role of TNF as mediator of the effects of endotoxin still remains uncertain. Furthermore, the present and other data suggest that TNF, like endotoxin, probably acts by an indirect mechanism against tumors in vivo.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D010586:Phagocytes / Q000502:physiology*; D010954:Plasmacytoma / Q000473:pathology*; D012513:Sarcoma, Experimental / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
D004731:Endotoxins; D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha