PERITONEAL AND SPLENIC MACROPHAGE FUNCTIONS IN THE TUMOR-BEARING HOST

In the tumor-bearing host, depression of cell-mediated immunity has be en well-demonstrated, but little is known about alterations in macroph age functions. We hypothesized that the presence of a tumor may cause functional suppression of peritoneal macrophage and splenic macrophage functions, perhaps due to prostaglandin-E(2) (PGE(2)) and nitric oxid e. C57 BL/6 mice (n = 18) were injected subcutaneously with Lewis lung carcinoma 3 tumor. Control mice (n = 18) received no tumor and were p air-fed to intake of the tumor group. On Day 21, peritoneal and spleni c macrophages were harvested. Cell surface Ia expression, cytotoxicity against P815 target cells, Candida albicans killing, and production o f PGE(2), nitric oxide, and superoxide were measured. Mean Ia expressi on was decreased in tumor animals for both peritoneal and splenic macr ophages. In tumor animals PGE(2) production significantly increased in both peritoneal and splenic macrophages. Superoxide production signif icantly decreased in peritoneal macrophages but significantly increase d in splenic macrophages. Nitric oxide production was also significant ly depressed in tumor-bearing host peritoneal macrophages. C. albicans killing was significantly depressed in tumor animals' peritoneal macr ophages but showed little change in splenic macrophages. In tumor anim als cytotoxicity was significantly decreased in peritoneal macrophages but significantly increased in splenic macrophages. In the tumor-bear ing host, peritoneal macrophages have significantly decreased accessor y and effector functions. Splenic macrophages demonstrate decreased ac cessory but enhanced effector functions. PGE(2), superoxide, and nitri c oxide appear to be important mechanisms of altered macrophage functi on in the tumor-bearing host; modifying their cellular production may enhance host defense. (C) 1995 Academic Press, Inc.