In vivo effects of toxic and detoxified endotoxin alone or in combination with muramyl dipeptide on lymphoid and non-lymphoid cells in the spleen of Meth A sarcoma-bearing mice.

In this study we confirmed that combinations of toxic or detoxified endotoxin with muramyl dipeptide (MDP) induced much more necrosis of transplanted Meth A sarcoma in mice than toxic endotoxin alone. Detoxified endotoxin and MDP alone had little antitumor effects. We investigated whether these divergent antitumor effects could be related to histopathological changes in the white pulp of the spleen of Meth A sarcoma-bearing mice. Toxic endotoxin reduced the T:B cell compartment ratio in the splenic white pulp by increasing the size of the B-cell compartment while leaving the size of the T-cell dependent inner PALS unaffected. The number of the T-lymphocytes in this area, however, was reduced. The border of B-lymphocytes in the marginal zone was markedly narrowed and the number of marginal metallophils along the inner border of the marginal sinus was decreased. None of these changes were observed after treatment with detoxified endotoxin or MDP. Addition of MDP to either endotoxin did not change their effects. The histopathological changes in the lymphoid and non-lymphoid compartments of the splenic white pulp are apparently exclusively induced by toxic endotoxin. As the antitumor activity of both toxic and detoxified endotoxin combined with MDP are about equal and more powerful than the activity of toxic endotoxin alone, it is concluded that these antitumor effects cannot be related to changes in the white pulp of the spleen.