Hastings K L, Thomas C, Brown A P, Gandolfi A J
Division of Antiviral Drug Products, U.S. Food and Drug Administration, Rockville, MD 20857, USA.
Immunopharmacol Immunotoxicol. 1995 Feb;17(1):201-13. doi: 10.3109/08923979509052729.
Halothane hepatitis appears to result from an inappropriate immune response to the products of halothane metabolism. Attempts to produce an animal model for halothane hepatitis have been largely unsuccessful. Although guinea pigs produce neoantigens following treatment with halothane, the subsequent antibody response is weak, possibly accounting for the failure to produce halothane hepatitis in these animals. In order to increase the antibody response to halothane neoantigens, three methods for trifluoroacetylating proteins were used. Guinea pigs were either treated with S-ethylthiotrifluoroacetate, autologous lymphocytes trifluoroacetylated ex vivo, or immunized with trifluoroacetylated mycobacterial protein, followed by exposure to halothane, and examined for anti-halothane metabolite antibodies (anti-TFA antibodies). Animals treated with S-ethylthiotrifluoroacetate developed anti-TFA antibodies, and following exposure to halothane exhibited an enhanced antibody response. Treatment with trifluoroacetylated lymphocytes also resulted in an enhanced anti-TFA antibody response following halothane exposure. Immunization with trifluoroacetylated mycobacterial proteins resulted in very high anti-TFA antibody titers. However, subsequent exposure to halothane had no observable effect on specific antibody titers. Exposure to halothane, regardless of treatment, resulted in the production of anti-microsomal protein antibodies. Signs of halothane hepatitis were not observed, indicating that enhancement of the humoral immune response does not appear to be sufficient for production of halothane hepatitis.
氟烷性肝炎似乎是由对氟烷代谢产物的不适当免疫反应引起的。建立氟烷性肝炎动物模型的尝试大多未成功。尽管豚鼠在接受氟烷治疗后会产生新抗原，但随后的抗体反应较弱，这可能是这些动物无法诱发氟烷性肝炎的原因。为了增强对氟烷新抗原的抗体反应，使用了三种使蛋白质三氟乙酰化的方法。给豚鼠分别用S - 乙基硫代三氟乙酸酯处理、离体三氟乙酰化自体淋巴细胞或用三氟乙酰化的分枝杆菌蛋白免疫，然后接触氟烷，并检测抗氟烷代谢物抗体（抗TFA抗体）。用S - 乙基硫代三氟乙酸酯处理的动物产生了抗TFA抗体，接触氟烷后抗体反应增强。用三氟乙酰化淋巴细胞处理也导致接触氟烷后抗TFA抗体反应增强。用三氟乙酰化分枝杆菌蛋白免疫导致抗TFA抗体滴度非常高。然而，随后接触氟烷对特异性抗体滴度没有可观察到的影响。无论是否经过处理，接触氟烷都会导致抗微粒体蛋白抗体的产生。未观察到氟烷性肝炎的迹象，这表明体液免疫反应的增强似乎不足以引发氟烷性肝炎。
