Trifluoroacetylation potentiates the humoral immune response to halothane in the guinea pig.
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.
Hastings
K L
KL
Division of Antiviral Drug Products, U.S. Food and Drug Administration, Rockville, MD 20857, USA.
Thomas
C
C
Brown
A P
AP
Gandolfi
A J
AJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005463:Fluoroacetates; D006168:Guinea Pigs; D006221:Halothane / Q000276:immunology* / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D009161:Mycobacterium / Q000276:immunology; D011506:Proteins / Q000276:immunology* / Q000378:metabolism*; D014269:Trifluoroacetic Acid / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D000941:Antigens; D001426:Bacterial Proteins; D005463:Fluoroacetates; D011506:Proteins; C028085:ethylthiol trifluoroacetate; D014269:Trifluoroacetic Acid; D000410:Alanine Transaminase; D006221:Halothane