Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice.

Animal 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 sevoflurane anaesthesia on the immune response in mice were studied. Sevoflurane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevoflurane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevoflurane 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, sevoflurane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.

[Effects of sevoflurane anesthesia on the immune response and biochemical parameters in mice. Comparison between single exposure and repeated anesthesia]. / Efectos de la anestesia con sevoflurano sobre la respuesta inmunitaria y parámetros bioquímicos en ratones. Comparación entre exposición única y anestesia reiterada.

OBJECTIVE: Given that anesthesia and surgery are known by their immunomodulatory effects, we aimed to compare the immune response after 1 or 3 anesthetic exposures to sevoflurane in a murine model without surgery. MATERIAL AND METHODS: Young adult male mice, non-controlled for body conformation, were exposed 1 (group S1) or 3 times (group S3) to 3% sevoflurane in oxygen (1.2 maximum alveolar concentration) for 40 minutes. Untreated animals were used as controls. Three days after in vivo exposure to sevoflurane, the cellular composition of peripheral blood and of the spleen were studied. We also studied the in vivo response to exogenous (sheep red blood cells: SRBC) and endogenous antigens (heat shock proteins: HSP 65 and HSP 70) as well as biomarkers of toxicity. RESULTS: The number of leukocytes in peripheral blood decreased in S3 animals, and the number of lymphocytes decreased in both groups. B cells in spleen decreased only in the S1 group, but an increased in vivo response to SRBC was seen in both S1 and S3 mice in comparison with the control animals. Re-exposure to sevoflurane led to a decrease in immunoglobulin G response only to HSP 70. Plasma markers of liver and kidney function did not change after anesthetic exposure. CONCLUSION: Changes in leukocyte populations in peripheral blood and in antibody-producing capacity occur after either a single exposure or repeated exposures to sevoflurane. However no changes occur in biomarkers of toxicity.