Demonstration of a cellular immune response in Halothane-exposed guinea pigs

Sylvia M. Furst, Dennis Luedke, Htoo Htoo Gaw, Richard Reich, A Jay Gandolfi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Halothane hepatitis is considered to be a result of an idiosyncratic autoimmune reaction brought about by the formation of neoantigens that have been generated by covalent binding of halothane biotransformation intermediates. The guinea pig is being examined as an animal model to investigate an immune-mediated mechanism for halothane hepatotoxicity. Male Hartley guinea pigs were exposed to 1% halothane/40% oxygen for 4 hr, three times with 40-day intervals. Kupffer cells and splenocytes were isolated from animals on various days after each halothane exposure. Splenocytes were cocultured in a lymphocyte transformation test with various concentrations of TFA(trifluoroacetylated)-antigens for 7 days and proliferation was measured by 3H-thymidine incorporation. In a second experiment, Kupffer cells were cocultured with autologous as well as allogeneic splenocytes with or without concanavalin A to determine whole cell sensitization and accessory function by Kupffer cells from treated animals. A 4-fold increase in splenocyte proliferation occurred in response to TFA-guinea pig albumin, No significant increase in proliferation could be detected with TFA-lysine or guinea pig albumin. A 14-fold increase in splenocyte proliferation also occurred in response to Kupffer cells from halothane-exposed animals, Autologous splenocytes demonstrated more of a response from treated versus control animals, indicating possible involvement of major histocompatibility complex II antigens. These results indicate recognition of TFA-antigens and Kupffer cells as antigen-presenting cells in halothane-exposed guinea pigs. This study provides good evidence that a cellular immune response is involved in the guinea pig after halothane exposure.

Original languageEnglish (US)
Pages (from-to)245-255
Number of pages11
JournalToxicology and Applied Pharmacology
Volume143
Issue number2
DOIs
StatePublished - Apr 1997

Fingerprint

Halothane
Cellular Immunity
Kupffer Cells
Guinea Pigs
Demonstrations
Animals
Antigens
Albumins
Antigen-Presenting Cells
Lymphocyte Activation
Concanavalin A
Biotransformation
Lymphocytes
Major Histocompatibility Complex
Accessories
Thymidine
Lysine
Animal Models
Oxygen

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Demonstration of a cellular immune response in Halothane-exposed guinea pigs. / Furst, Sylvia M.; Luedke, Dennis; Gaw, Htoo Htoo; Reich, Richard; Gandolfi, A Jay.

In: Toxicology and Applied Pharmacology, Vol. 143, No. 2, 04.1997, p. 245-255.

Research output: Contribution to journalArticle

Furst, Sylvia M. ; Luedke, Dennis ; Gaw, Htoo Htoo ; Reich, Richard ; Gandolfi, A Jay. / Demonstration of a cellular immune response in Halothane-exposed guinea pigs. In: Toxicology and Applied Pharmacology. 1997 ; Vol. 143, No. 2. pp. 245-255.
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