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.