Cytokine-induced production of NO by macrophages induces apoptosis and immunological rejection of AK-5 histiocytic tumor

The immunological rejection of the AK-5 histiocytoma in syngeneic hosts involves the participation of NK cells and the upregulation of Th1 type cytokine response. The tumor cells are killed by necrosis and apoptosis. We have studied the role of host peritoneal macrophages in tumor regression. Activated macrophages from tumor- bearing animals produce cytokines like IL-1, TNF-, IL-12 and free radicals like nitric oxide during tumor regression. IL-12 and IFN- played a crucial role in the induction of NO production by the host macrophages, since administration of anti IL-12 and anti IFN- antibodies in AK-5 tumor-bearing animals suppressed NO production by the macrophages. Similarly the cytotoxic activity of the host macrophages which is dependent on NO production was also affected in antibody injected animals. These studies indicate an important role for cytokines in the activation of host macrophages which in turn produce nitric oxide that is involved in the induction of apoptosis in AK-5 cells, leading to the regression of the tumor.