HALOGENATED ANESTHETICS FORM LIVER ADDUCTS AND ANTIGENS THAT CROSS-REACT WITH HALOTHANE-INDUCED ANTIBODIES

Two halogenated anesthetics, enflurane and isoflurane, have been assoc iated with an allergic-type hepatic injury both alone and following pr evious exposure to halothane. Halothane hepatitis appears to involve a n aberrant immune response. An antibody response to a protein-bound bi otransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cr oss-reactivity between enflurane and isoflurane with the hypersensitiv ity induced by halothane. The subcellular and lobular production of he patic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoanti gens was investigated in two animal models. Enflurane administration r esulted in neoantigens detected in both the microsomal and cytosolic f raction of liver homogenates and in the centrilobular region of the li ver. In the same liver, biochemical analysis detected fluorinated live r adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could pro duce a hypersensitivity conditio n similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to thes e antigens.