Methylprednisolone injection via the portal vein suppresses inflammation in acute liver failure induced in rats by lipopolysaccharide and d-galactosamine.
BACKGROUND
We have reported that hepatic arterial steroid injection is an effective therapy to rescue patients from fulminant or severe acute hepatic failure. We speculate that a high concentration of steroid suppresses inflammatory processes in the liver directly by restraining activated inflammatory cells, including macrophages. To analyse the detailed mechanism, steroid injection via the portal vein was performed in an experimental model of liver damage.


METHODS
Rats subjected to lipopolysaccharide and d-galactosamine injection were treated with a methylprednisolone injection via the tail vein or the portal vein. The survival rate, serum levels of inflammatory cytokines and apoptotic cell counts in the liver were analysed.


RESULTS
The survival rate was significantly improved by steroid injection, especially via the portal vein. Serum values of alanine aminotransferase, tumor necrosis factor-alpha and interferon-gamma were reduced in the treated groups, especially the group given portal venous injections. Apoptotic cell counts in the liver were significantly lower in the group injected with steroid via the portal vein.


CONCLUSIONS
In the model rats, high concentrations of steroid in the liver acted on inflammatory cells and suppressed inflammatory cytokines and liver cell death. The mechanism is suggested to be the same for arterial steroid injection therapy in patients with acute hepatic failure.
Higuchi
Nobito
N
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka, Japan.
Kato
Masaki
M
Kotoh
Kazuhiro
K
Kohjima
Motoyuki
M
Aishima
Shinichi
S
Nakamuta
Makoto
M
Fukui
Yoshinori
Y
Takayanagi
Ryoichi
R
Enjoji
Munechika
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005688:Galactosamine; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000097:blood; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008776:Methylprednisolone Hemisuccinate; D005688:Galactosamine; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase