Muramyl dipeptide is a powerful potentiator of the antitumor action of various tumor-necrotizing agents

Abstract

The previously observed potentiation of necrosis and regression of solid immunogenic Meth A sarcoma transplants in mice after IV administration of endotoxin by addition of muramyl dipeptide (MDP) in saline was investigated further by varying time and route of administration of both agents. Equal potentiation was observed when MDP was administered 4 h before or after endotoxin, but administration 48 h or 24 h before or 24 h after endotoxin had no effect. Simultaneous administration of both agents enhanced tumor damage considerably, regardless of the route of administration of either agent. A strong potentiation of necrosis and regression was also observed upon addition of MDP to concanavalin A, poly I:C or poly A:U and, to a lesser degree, to a radio-detoxified endotoxin, purified L cell interferon, or Propionibacterium acnes. No consistent relationship could be seen between the degree of potentiation of necrosis and of regression. It was suggested that distinct mechanisms underlie the augmenting action of MDP on necrosis and regression and that enhanced production and/or action of vasoactive agents might play a role in the potentiation of necrosis. Whether the capacity of MDP to stimulate specific and nonspecific immune defense is involved in the enhancement of tumor regression remains uncertain at present.