We investigated the effect of Ulmi radicis cortex extract (UrCE) on the pro
duction of nitric oxide (NO). Stimulation of mouse peritoneal macrophages w
ith UrCE after the treatment of recombinant interferon-gamma (rIFN-gamma) r
esulted in the increased NO synthesis. UrCE had no effect on NO synthesis b
y itself. When UrCE was used in combination with rIFN-gamma, there was a ma
rked cooperative induction of NO synthesis in a dose-dependent manner. The
optimal effect of UrCE on NO synthesis was shown 6 h after treatment with r
IFN-gamma. NO production was inhibited by N-G-monomethyl-L-arginine. The in
creased production of NO from rIFN-gamma plus UrCE-stimulated cells was dec
reased by the treatment of protein kinase C inhibitor such as staurosporin.
In addition, synergy between rIFN-gamma and UrCE was mainly dependent on U
rCE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the prep
arations of UrCE were endotoxin free. These results suggest that the capaci
ty of UrCE to increase NO production from rIFN-gamma-primed mouse peritonea
l macrophages is the result of UrCE-induced TNF-alpha secretion.