Propionibacterium acnes induces acute TNF alpha-mediated apoptosis of hepatocytes followed by inflammatory T-cell-mediated granulomatous hepatitis inmice

The CD3+/TCR alpha beta+ T-cell-mediated hepatic inflammation induced by Pr opionibacterium acnes could be divided into an acute and a chronic phase. T he acute phase occurred within 72 h after injection and displayed hepatic a poptosis. Anti-TNF alpha antibody inhibited both the P. acnes-induced hepat ic apoptosis and lymphocyte infiltration seen in this phase, indicating the involvement of this cytokine, Thereafter, a chronic phase was manifested f rom days 7 to 44 after injection. it was characterized as granulomatous inf lammation admired with apoptosis of infiltrating lymphocytes and some hepat ocytes. Immunohistochemical staining showed that the infiltrating lymphocyt es displayed TNF alpha, TNF type I receptor and a variety of cytokines incl uding IL-1 beta, IL-4, IL-6, IL-10, IFN gamma or IL-12. Interestingly, in n aive mice, the arteries in the liver constitutively expressed IFN gamma. It s expression appeared to be substantially increased at 48 h, decreased at 7 2 h, and increased again on day 14 after P. acnes injection. Furthermore, F as or Fast was only detected on the lymphocytes within the granuloma, We co nclude that P. acnes can induce a TNF alpha-mediated acute hepatic apoptosi s which subsequently progress to a T-cell-mediated granulomatous hepatitis with increased expression of multiple cytokines and Fas/FasL.