Immunomodulatory activity of TNF-alpha during acute liver injury induced by D-galactosamine and its protection by PGE1 in rats.
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| Abstract |
Tumour necrosis factor-alpha (TNF-alpha) mediates hepatocyte cell death by D-galactosamine (D-GalN) and its protection by prostaglandin E(1) (PGE(1)). The activation of immune system plays an important role in the development of liver injury. TNF-alpha and PGE(1) regulate the activity and cytokine release of different inflammatory cells. The present study was undertaken to determine if the noxious or hepatic protective properties of TNF-alpha during D-GalN-induced liver injury was related to an alteration by PGE(1) of the immunoregulatory activity of TNF-alpha. The role of TNF-alpha was assessed by anti-TNF-alpha antibodies to D-GalN-treated rats in the presence or absence of PGE(1). D-GalN enhanced the percentage of monocytes and T lymphocytes in the total peripheral blood mononuclear cells (PBMCs). D-GalN enhanced the activation degree of monocytes, but reduced that of T lymphocytes. D-GalN also enhanced TNF-alpha, IL-1alpha, IL-6 and IFN-gamma concentrations in blood. Anti-TNF-alpha antibodies abolished all immunological changes and greatly reduced liver damage induced by D-GalN. The protection by PGE(1) against D-GalN liver injury was associated with an increase in TNF-alpha concentration and a reduction of IL-1alpha and IL-6. These changes were associated with a reduction of monocyte activation degree and a recovery of that of T lymphocytes. Although anti-TNF-alpha antibodies abolished the protection by PGE(1) against D-GalN-liver injury, they did not essentially counteract the effect of the prostanoid in all immunological parameters studied. The present study showed that the protection against D-GalN liver damage by PGE(1) or anti-TNF-alpha was associated with similar effects on the inflammatory parameters studied. Nevertheless, the abolishment of liver protection by PGE(1) with anti-TNF-alpha in D-GalN-treated rats in the presence of a protective cytokine profile suggests that the release of TNF-alpha induced by PGE(1) pre-administration was exerting a direct protective effect on hepatocytes against D-GalN injury. Consequently, the effect of PGE(1) on inflammatory parameters studied during liver injury was unrelated to TNF-alpha.
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| Authors | José Manuel Lozano, Javier Padillo, José Luis Montero, José Peña, Manuel De la Mata, Jordi Muntané |
| Journal | International immunopharmacology (Int Immunopharmacol) Vol. 3 Issue 2 Pg. 197-207 (Feb 2003) ISSN: 1567-5769 [Print] Netherlands |
| PMID | 12586601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright 2003 Elsevier Science B.V. |
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