TRIFLUOROACETYLATION POTENTIATES THE HUMORAL IMMUNE-RESPONSE TO HALOTHANE IN THE GUINEA-PIG

Halothane hepatitis appears to result from an inappropriate immune res ponse to the products of halothane metabolism. Attempts to produce an animal model for halothane hepatitis have been largely unsuccessful. A lthough guinea pigs produce neoantigens following treatment with halot hane, the subsequent antibody response is weak, possibly accounting fo r the failure to produce halothane hepatitis in these animals. In orde r to increase the antibody response to halothane neoantigens, three me thods for trifluoroacetylating proteins were used. Guinea pigs were ei ther treated with S-ethylthiotrifluoroacetate, autologous lymphocytes trifluoroacetylated ex vivo, or immunized with trifluoroacetylated myc obacterial protein, followed by exposure to halothane, and examined fo r anti-halothane metabolite antibodies (anti-TEA antibodies). Animals treated with S-ethylthiotrifluoroacetate developed anti-TEA antibodies , and following exposure to halothane exhibited an enhanced antibody r esponse. Treatment with trifluoroacetylated lymphocytes also resulted in an enhanced anti-TEA antibody response following halothane exposure . Immunization with trifluoroacetylated mycobacterial proteins resulte d in very high anti-TFA antibody titers. However, subsequent exposure to halothane had no observable effect on specific antibody titers. Exp osure to halothane, regardless of treatment, resulted in the productio n of anti-microsomal protein antibodies. Signs of halothane hepatitis were not observed, indicating that enhancement of the humoral immune r esponse does not appear to be sufficient for production of halothane h epatitis.