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SummaryAnimal and technical models often require repeated anaesthetic administrations for surgical procedures. As there is evidence for immunomodulatory effects of anaesthesia, the effects of repeated exposure to sevo urane anaesthesia on the immune response in mice were studied. Sevo urane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevo urane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevo urane anaesthesia, peripheral blood leukocyte counts, the composition and in vitro function of spleen cells (lymphocytes and macrophages) and the in vivo immune response to a conventional T-dependent antigen were assessed. In addition, liver, spleen and kidney histopathology and also hepatic and renal function were studied. Three days after the latest anaesthetic procedure, the absolute number of both leukocyte and lymphocyte counts were reduced in peripheral blood. Splenic cell composition (LB, LTCD3‡ , LTCD4 ‡ and LTCD8 ‡ ), macrophage function and the mitogen-induced lymphoprolipherative response were preserved. Yet, the in vivo humoral response to a conventional antigen was augmented following the antigenic challenge. Assessment at day 9 after the last anaesthetic procedure revealed the persistence of the humoral response alteration. Nevertheless, sevo urane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.

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The effect of halothane anesthesia on the humoral immune response to sheep red blood cells was studied in mice immunized twice, with a 15-day interval. On both occasions, mice were exposed to 1.5% halothane for 40 min immediately after sensitization. Halothane reexposure resulted in increased numbers of IgG-secreting cells (IgG-SC) as well as circulating 7S-serum agglutinins. To examine further whether this effect could be obtained in syngeneic recipients, adoptive transfer experiments employing spleen cells were performed. While mice receiving cells from unimmunized and anesthetized donors displayed significantly higher levels of IgG-SC, recipients of cells from normal, immunized and immunized-anesthetized donors showed a depressed response when compared to control counterparts. Besides the possibility of an enhancing effect of halothane reexposure on the humoral response, this procedure may counteract normal physiological immunoregulatory processes during the generation of the immune response.

The impact that reexposure to anesthetics delivered in 100% oxygen or in synthetic air (21% oxygen/79% nitrogen) has on the secondary humoral immune response to sheep red blood cells was studied. Mice were immunized twice with a 15-day interval and anesthetized immediately after each antigenic challenge with 1.5% halothane or 1.5% isoflurane for 40 min. Halothane in oxygen resulted in increased numbers of IgG-secreting cells (IgG-SC), while halothane in air depressed the response when compared to control mice. In contrast, isoflurane vaporized in oxygen did not affect IgG-SC numbers, while isoflurane given in air lowered the response. Furthermore, neither 100% oxygen, nor the stress of being in an anesthesia chamber breathing synthetic air for 40 min had any immunological effect in non-anesthetized mice. The inspired oxygen concentration during halothane or isoflurane anesthesia has an effect on the secondary immune response. The effect is different between halothane and isoflurane, possibly due to differences in the extent of their metabolic and pharmacodynamic properties.