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.