Mes. Ferreira et al., Role of the hepatic function in the development of the pyrogenic toleranceto muramyl dipeptide, AM J P-REG, 281(1), 2001, pp. R162-R169
Citations number
45
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
We have demonstrated that the hepatic function may have an important role i
n the development of tolerance to the pyrogenic effect induced by endotoxin
. To further investigate if the role of the hepatic function in the develop
ment of tolerance also extends to that induced by other pyrogenic stimuli,
we investigated the effect of galactosamine, a specific inhibitor of the he
patic protein synthesis, on the development of tolerance to the pyrogenic e
ffect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was o
bserved after the second intravenous or intraperitoneal injection of MDP (5
00 mug/kg), 24 h after the first injection, similar to what was observed wi
th endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/
kg ip) was injected simultaneously with MDP (500 mug/kg iv) on the first da
y. When uridine (600 mg/kg ip) was administered simultaneously with galacto
samine (300 mg/kg ip) and the first injection of MDP (500 mug/kg ip), pyrog
enic tolerance was again observed after the second injection of the peptido
glycan. In conclusion, the hepatic function may not be important only for t
he development of tolerance to endotoxin, but also to a totally different p
yrogenic stimulus such as MDP.