EVIDENCE INCONSISTENT WITH A ROLE FOR TUMOR NECROSIS FACTOR IN TUMOR ALLOGRAFT REJECTION

Abstract

Since it has been suggested that tumor necrosis factor is involved in organ allograft rejection, experiments were undertaken to determine whether it is involved in the rejection of allogeneic P815 tumor cells growing as ascites in the peritoneal cavities of mice. The results show that biologically active TNF was not detectable in serum or ascites fluid of mice during either growth or vigorous rejection of the tumor. On the other hand, mice in the process of rejecting their ascites tumor displayed a greatly enhanced capacity to produce TNF in the peritoneal cavities and systemically in response to an injection of endotoxin i.p. These results show that the immune response to the tumor was associated with the priming of host cells for increased TNF production both locally and systemically in response to an appropriate stimulus that was not supplied during the generation and expression of immunity. Additional evidence against a role for TNF in ascites tumor allograft rejection is seen in the finding that i.p. administration of anti-TNF antibodies failed to interfere with elimination of allogeneic tumor cells, even though the antibodies were given repeatedly before and during the rejection process. Taken together, these results are inconsistent with the view that TNF is involved in the effector stage of the anti-allograft response, even though cells at the site of rejection are primed to produce large quantities of TNF in response to endotoxin.