Quantitative histology of muramyl dipeptide-potentiated induction of tumor necrosis by endotoxins.

Abstract

Combinations of muramyl dipeptide (MDP) and toxic or detoxified endotoxin induced necrosis and subsequent disappearance of solid Meth A tumors in syngeneic mice. Toxic endotoxin alone was far less effective. MDP and detoxified endotoxin had negligible antitumor effects of their own. These observations were confirmed by histological examination. Neither MDP nor detoxified endotoxin induced significant changes in and around the tumor by 4, 24, and 48 h after intravenous administration when compared with saline treatment. MDP amplified various effects of toxic endotoxin such as the induction of hyperemia, mitotic arrest, mast cell depletion, non-hemorrhagic necrosis and reduction in lymphocyte infiltrates, but did not affect hemorrhagic necrosis or the influx of polymorphonuclear leukocytes. The combination of MDP and detoxified endotoxin lacked the latter two effects, but the other effects were similar to, although slightly less marked than those induced by the toxic combination. Because the degree of hyperemia was proportional to the degree of subsequent non-hemorrhagic necrosis, MDP seems to potentiate necrosis by enhancing mechanisms leading to hyperemia and mast cell mediators might be involved in the latter effect. Lymphocyte influx and the therapeutic outcome are likely to be related, since exclusively therapeutic treatments reduced the influx of these cells.