Halothane hepatitis: attempt to develop an animal model

Patients with liver damage following halothane anaesthesia (halothane hepatitis) have circulating antibodies reacting with plasma membrane determinants present on hepatocytes isolated from rabbits previously exposed to halothane. In an attempt to develop an animal model of halothane hepatitis, rabbits were immunised with hepatocytes isolated from litter mates previously exposed to halothane; this resulted in the generation of antibodies to both normal and halothane related liver cell determinants detected by both immunofluorescence and indirect cytotoxicity. Exposure of these immunised rabbits to halothane resulted in the disappearance of the halothane-related antibody, presumably due to its reaction with the liver-cell membrane halothane-related antigen; this, however, could not be proved since immunisation with halothane hepatocytes induced the presence of antibodies on the recipient hepatocytes. Although both human and rabbit lymphocytes were directly cytotoxic in vitro to these antibody coated hepatocytes, no evidence of liver damage could be detected. Thus, if immune mechanisms are involved in the pathogenesis of halothane hepatitis, other factors, probably related to idiosyncratic host immune responses, must be implicated.