TNF-alpha but not IL-1alpha are Correlated with PGE₁-Dependent Protection Against Acute D-Galactosamine-Induced Liver Injury

Abstract

BACKGROUND: Prostaglandin E₁ (PGE₁) treatment of humans and rodents during acute hepatic failure ameliorates different parameters of hepatic dysfunction.PURPOSE: To investigate whether prevention of acute liver injury induced by D-galactosamine (D-GalN) with preadministration of PGE₁ is correlated with a change in the concentration of two proinflammatory cytokines, as tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1α, and/or nitrite+nitrate (NOx), as nitric oxide-related end products in serum.RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and TNF- αconcentration in serum 5 and 10 mins, respectively, after treatment compared with the control group (P≤0.05). D-GalN did not change the IL-1α concentration at any time during the study. Preadministration of PGE₁ to D-GalN-treated rats significantly reduced the ALT content and increased significantly the TNF-α concentration in serum 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN group (P≤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 increased TNF-α release. Preadministration of PGE₁ to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels of TNF-α but not IL-1α. These findings indicate that stimulation of TNF-α release may be involved in the acute D-GalN-induced liver injury and also in PGE₁ protection from hepatotoxicity in clinical and experimental studies.