INHIBITION OF INTERFERON STIMULATION OF NATURAL-KILLER-CELL ACTIVITY IN MICE ANESTHETIZED WITH HALOTHANE OR ISOFLURANE

Background: Basal cytotoxic activity of NK cells, a subtype of lymphocytes involved in the nonspecific immune response to viruses, tumors, and some bacteria, is altered in the postoperative period. The current study examines the effects of halothane and isoflurane on interferon-induced stimulation of NK cell cytotoxicity in vivo and in vitro. Methods: Mice were exposed to either anesthetic on days 10, 5, 1, or -1 relative to interferon treatment on day 0. NK cytotoxicity was assessed 24 h later. Similarly, splenic mononuclear cells containing NK cells were treated with interferon, before or after in vitro exposure with either halothane or isoflurane, and cytotoxicity was determined. Results: In vivo, isoflurane or halothane inhibited subsequent interferon-induced NK cell stimulation (>90% and 67%, respectively). No inhibition occurred if interferon was given before anesthetic exposure. Significant inhibition of interferon-induced NK cell stimulation could be observed 11 days after anesthesia. In vitro, both anesthetics inhibited the subsequent stimulation of NK cytotoxicity by interferon, however, cytotoxicity of NK cells treated with interferon before anesthetic exposure was comparable to untreated interferon-stimulated NK cells. Conclusions: Halothane and isoflurane inhibit interferon stimulation of NK cytotoxicity in naive (unstimulated) NK cells of the splenic mononuclear cell pool without affecting the cytotoxicity of previously stimulated (interferon) NK cells. This could occur directly by preventing the NK cell from responding or indirectly by altering other cells in the splenic mononuclear cell pool (T cells, macrophages), which then inhibit NK cell induction.