title: Infliximab exerts no direct hepatotoxic effect on HepG2 cells in vitro.
abstract: BACKGROUND
  Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed.
  
  
  OBJECTIVE
  The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of principle the in vitro toxicity of thiopurines and methotrexate was also determined.
  
  
  METHODS
  Cell survival curves and the half maximal inhibitory concentrations (IC(50)) were obtained after 24, 48 and 72 h of incubation in HepG2 cells with the IBD drugs azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate or infliximab by using the WST-1 cytotoxicity assay.
  
  
  RESULTS
  No in vitro hepatotoxicity in HepG2 cells was seen with infliximab, while concentration-dependent cytotoxicity was observed when HepG2 cells were incubated with increasing concentrations of azathioprine, 6-mercaptopurine and 6-thioguanine.
  
  
  CONCLUSIONS
  Infliximab alone or given in combination with azathioprine showed no direct hepatotoxic effect in vitro, indicating that the postulated direct hepatotoxicity of infliximab is unlikely.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. h.devries@MDL.umcn.nl
authors.forename: Hilbert S
authors.initials: HS
authors.lastname: de Vries
authors.forename: Tineke
authors.initials: T
authors.lastname: de Heij
authors.forename: Henie M J
authors.initials: HM
authors.lastname: Roelofs
authors.forename: Rene H M
authors.initials: RH
authors.lastname: te Morsche
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: de Jong
mesh_terms: D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000633:toxicity*; D001379:Azathioprine / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells / Q000187:drug effects*; D018197:Hepatoblastoma / Q000139:chemically induced; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy; D000069285:Infliximab; D008113:Liver Neoplasms / Q000139:chemically induced; D015122:Mercaptopurine / Q000494:pharmacology / Q000633:toxicity; D008727:Methotrexate / Q000494:pharmacology / Q000633:toxicity; D012680:Sensitivity and Specificity; D013866:Thioguanine / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D000069285:Infliximab; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine; D008727:Methotrexate