title: Effect of rifampin on production of inflammatory mediators in HepG2 liver epithelial cells.
abstract: Rifampin, a potent antibacterial agent, is one of the main drugs used in the treatment of mycobacterial infections. Hepatotoxicity is a well-documented adverse event. The aim of this study was to investigate the effect of rifampin on the production of inflammatory mediators in human epithelial HepG2 liver cells in the absence or presence of proinflammatory cytokines. Incubation of HepG2 cells with a cytokine mix plus rifampin was associated with a significant dose-dependent increase in the production of nitric oxide compared to incubation with the cytokine mix alone (P < 0.05) as well as with an increase in inducible nitric oxide synthase protein and mRNA expression. Rifampin significantly increased the secretion of interleukin 8 (IL-8) in both untreated cells (P < 0.001) and cytokine-treated cells (P < 0.006). An array screening assay revealed that rifampin stimulated the production of IL-1β and gamma interferon-induced protein-10 (IP-10) in untreated cells and increased the secretion of RANTES in cytokine-treated cells. Together, these results indicate that rifampin may exert proinflammatory effects on liver cells.
authors.affiliation: Laboratory of Infectious Diseases, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva 49100, Israel. yuhas@post.tau.ac.il
authors.forename: Yael
authors.initials: Y
authors.lastname: Yuhas
authors.forename: Eva
authors.initials: E
authors.lastname: Berent
authors.forename: Shai
authors.initials: S
authors.lastname: Ashkenazi
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D056945:Hep G2 Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D012293:Rifampin / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D009569:Nitric Oxide; D012293:Rifampin