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I.p. or i.v. administration of Corynebacterium parvum (CP) to MF1 mice induces a generalized inflammatory response, associated with marked hepatosplenomegaly and accompanied by a pronounced granulomatous response in the liver. Injection of the Landschütz ascites carcinoma (LAC) 24 h after CP substantially reduced the intensity of the inflammatory response, and decreased both the frequency and size of the hepatic granulomas, as revealed by morphometric analysis of histological sections. The difference in cellular composition of the granulomas between the experimental groups, as revealed by light microscopy, was further emphasized and characterized by ultrastructural studies. These revealed the predominance of macrophages within the granulomas in tumour-bearing mice, in contrast to the predominance of epithelioid cells in the lesions which developed in mice given CP alone. Our experimental findings show that the inhibitory effect of the growing LAC on granuloma formation in response to CP cannot be ascribed to (a) sequestration of the microorganism within the growing tumour, (b) a nonspecific inflammatory stimulus, (c) diversion and seqestration of mononuclear phagocytes in the growing tumour or (d) the presence of lactate dehydrogenase-elevating virus in either the host or tumour cells. The inhibition of liver granuloma formation is consistent with an effect mediated by soluble, heat-stable tumour-associated factor(s).

I.p. administration of 1.4 mg Corynebacterium parvum (C. parvum) 24 h before inoculation of Landschütz ascites carcinoma (LAC) cells significantly impaired growth of the tumour in MF1 mice. The injection of tumour cells caused a transient inhibition of the activity of the mononuclear phagocyte system (MPS) in both normal and C. parvum-treated hosts, as evidenced by impaired clearance of colloidal carbon from the bloodstream and reduction in hepatic phagocytosis of 51Cr-labelled sheep erythrocytes. Depression in Kupffer-cell activity was associated with a shift in particle distribution towards the spleen. The pronounced hepatosplenomegaly in response to C. parvum was significantly less in animals which also received tumour cells. Histological examination of liver and spleen revealed evidence of depressed MPS activity. Granuloma production in the liver in response to C. parvum was inhibited in tumour-bearing mice, and macrophage proliferation within the spleen was also reduced. Ascitic fluid showed similar inhibitory effects to those of tumour-cell suspensions, suggesting production by LAC of a heat-stable macrophage-inhibitory factor.

Aprotinin was bound and endocytosed by Landschütz ascites carcinoma (LAC) cells in vitro. Addition of the antiprotease to cultures of these cells led to a dose-dependent growth-inhibitory and cytotoxic effect. In mice inoculated with LAC cells and treated with aprotinin there was a transient reduction in both the number and concentration of recovered ascites cells during the early phase of tumour growth. This was accompanied by a temporary increase in the proportion of peritoneal phagocytes (mononuclear phagocytes and polymorphonuclear leucocytes) relative to carcinoma cells. However, the number and concentration of ascites cells eventually achieved was comparable in saline and aprotinin-treated animals.

Growth of the Walker 256 carcinosarcoma implanted within various sites in Spraque-Dawley rats was investigated in animals receiving twice daily i.p. injections of the antiprotease aprotinin. Although administration of aprotinin partially attenuated the growth and lethality of i.p. tumour, no effect of aprotinin was found on intramuscular tumour development. Furthermore, we were unable to demonstrate unequivocal growth inhibition by aprotinin of lung tumour colonies from i.v. injection of tumour cells. Histological examination of intramuscular and pulmonary tumours revealed little evidence of host cellular immune response in either saline- or aprotinin-treated rats.