TNF-alpha but not IL-1 alpha is correlated with PGE(1)-dependent protection against acute D-galactosamine-induced liver injury

Citation
J. Muntane et al., TNF-alpha but not IL-1 alpha is correlated with PGE(1)-dependent protection against acute D-galactosamine-induced liver injury, CAN J GASTR, 14(3), 2000, pp. 175-180
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
CANADIAN JOURNAL OF GASTROENTEROLOGY
ISSN journal
0835-7900 → ACNP
Volume
14
Issue
3
Year of publication
2000
Pages
175 - 180
Database
ISI
SICI code
0835-7900(200003)14:3<175:TBNIAI>2.0.ZU;2-1
Abstract
BACKGROUND: Prostaglandin E-1 (PGE(1)) treatment of humans and rodents duri ng acute hepatic failure ameliorates different parameters of hepatic dysfun ction. PURPOSE: To investigate whether prevention of acute liver injury induced by D-galactosamine (D-GalN) with preadministration of PGE(1) is correlated wi th a change in the concentration of two proinflammatory cytokines, as tumou r necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 alpha, and/or ni trite+nitrate (NOx), as nitric oxide-related end products in serum. RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and TNF-alpha concentration in serum 5 and 10 mins, respectively, after treatme nt compared with the control group (P less than or equal to 0.05). D-GalN d id not change the IL-1 alpha concentration at any time during the study. Pr eadministration of PGE(1) to D-GalN-treated rats significantly reduced the ALT content and increased significantly the TNF-alpha concentration in seru m 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN gro up (P less than or equal to 0.05). Nitric oxide was not involved in either the toxic effect due to D-GalN or the protection observed with PGE1 against D-GalN toxicity. CONCLUSIONS: Acute liver injury induced by D-GalN is correlated with an inc reased TNF-alpha release. Preadministration of PGE1 to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels o f TNF-alpha but not IL-1 alpha. These findings indicate that stimulation of TNF-alpha release may be involved in the acute D-GalN-induced liver injury and also in PGE(1) protection from hepatotoxicity in clinical and experime ntal studies.