title: TNF-alpha but not IL-1alpha is 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.
  
  
  OBJECTIVE
  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-alpha) and interleukin (IL)-1alpha, and/or nitrite+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 treatment compared with the control group (P< or =0.05). D-GalN did not change the IL-1alpha 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-alpha concentration in serum 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN group (P< or =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-alpha release. Preadministration of PGE1 to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels of TNF-alpha but not IL-1alpha. These findings indicate that stimulation of TNF-alpha release may be involved in the acute D-GalN-induced liver injury and also in PGE1 protection from hepatotoxicity in clinical and experimental studies.
authors.affiliation: Hospital Universitario Reina Sofía, Córdoba, Spain. jmuntane@sofia.hrs.sas.cica.es
authors.forename: J
authors.initials: J
authors.lastname: Muntané
authors.forename: J L
authors.initials: JL
authors.lastname: Montero
authors.forename: J M
authors.initials: JM
authors.lastname: Lozano
authors.forename: A
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.forename: M
authors.initials: M
authors.lastname: de La Mata
authors.forename: G
authors.initials: G
authors.lastname: Miño
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D005688:Galactosamine; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D000410:Alanine Transaminase; D000527:Alprostadil