Y. Ishiwata et al., Protection against concanavalin A-induced murine liver injury by the organic germanium compound, propagermanium, SC J IMMUN, 48(6), 1998, pp. 605-614
Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium
compound that activates the immune system. In this study, we investigated t
he action of propagermanium on T-cell-mediated murine hepatic injury induce
d by concanavalin A (ConA). Oral administration of propagermanium inhibited
the development of liver injury about 10 h after ConA injection. Histologi
cal analysis demonstrated that propagermanium attenuated the extent of live
r damage compared with controls, reducing infiltration by leucocytes, espec
ially CD11b-positive cells. Infiltration by CD4-positive cells was not affe
cted. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are cru
cial for the development of hepatitis in this model. Propagermanium treatme
nt induced significant inhibition of subsequent TNF-alpha production about
10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-1
0, IL-4 and IL-12 production. This effect on TNF-production coincided with
the inhibition of aminotransferase activity late in the progression of Con
A-induced liver injury. These facts suggest that this compound affects the
macrophages (M phi) function in the liver sinusoid. Therefore, M phi were c
ultured with liver sinusoidal endothelial cells (SEC) and the effect of pro
pagermanium on TNF-alpha production in the presence of IFN-gamma was determ
ined. TNF-alpha production was reduced significantly in the coculture of M
phi and SEC when M phi was treated with propagermanium. These results might
explain the mechanisms by which propagermanium inhibits Con-A-induced live
r injury. That is, propagermanium improves hepatitis through mechanisms inc
luding the reduced production of TNF-alpha, without modification of Th1- an
d Th2-cell function.