ABSTRACT
Female CBi mice subjected to multiple exposures to halothane inhalation anesthesia before mating were investigated for the potential effects of such intervention on a specific antibody response mounted by them and their offspring. An assessment of the toxicologic and reproductive performance of female mice undergoing anesthesia was also performed. Adult female mice received three episodes of halothane anesthesia at weekly intervals. Seventy-two hours after the last dose, mice were subjected to the following procedures: 1) study of the specific humoral immune response to sheep red blood cells (SRBC); 2) hematologic, hepatologic, and histopathologic studies; and 3) mating with syngeneic sires. Halothane-treated females had increased amounts of specific antibody secreting B cells, with liver studies showing evidence of microscopic fatty changes and decreased lipid peroxidation. Anesthesia did not alter reproductive performance but lowered offspring survival. Offspring displayed depressed antibody response after challenge with SRBC at weaning and at 60 d of age. The anti-SRBC antibody response that was found to be enhanced in halothane anesthetized females, seemed to be conversely impaired when studied in the offspring.
Subject(s)
Anesthetics, Inhalation/toxicity , Halothane/toxicity , Immune System/drug effects , Reproduction/drug effects , Animals , Antibody Formation/drug effects , Antibody-Producing Cells/drug effects , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Blood Cell Count/drug effects , Erythrocytes/immunology , Female , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Lipid Peroxidation/drug effects , Liver/drug effects , Male , Mice , Mice, Inbred Strains , Organ Size/drug effects , Pregnancy , Spleen/immunology , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The extent of surgery, the patient's age, health status and other factors may contribute to alteration of the immune system during anesthesia and surgery. In addition, inhalatory anesthetics may cause acute and chronic toxicity because of the production of intermediate and end metabolic compounds. The present work was undertaken to evaluate, both in vivo and in vitro, if repeated doses of halothane were able to affect the immune response in a murine model developed at our laboratory. Weekly doses of halothane were administered to mice subjected to no surgery and three days after the last anesthetic-exposure, several immunologic parameters were assessed. Results on the in vivo response to sheep red blood cells showed that halothane treatment increased the amount of specific antibody secreting B-cells, without affecting the delayed type hypersensitivity reaction to the same antigen. In vitro studies on spleen cell composition showed that halothane re-exposure diminished the number of CD4+, CD8+ and B-cells. Such changes were not translated into alterations on the mitogen-driven lymphoproliferation, as well as macrophage phagocytic and lytic functions. Our results indicate that halothane re-exposure is able to modulate the immune response affecting both the number of antibody secreting cells involved in a specific in vivo response, and the splenic lymphoid cell composition. Since such halothane-induced immune alterations might bias the results of a wide range of physiological research, even those involving other systems, a careful selection of the anesthetic agent and methods by which the compound is administered is advisable.
Subject(s)
Anesthetics, Inhalation/pharmacology , Halothane/pharmacology , Spleen/drug effects , Animals , Lymphocyte Subsets/drug effects , Lymphocytes/drug effects , Lymphocytes/immunology , Male , Mice , Mice, Inbred Strains , Phagocytosis/drug effects , Spleen/immunologyABSTRACT
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.
Subject(s)
Anesthetics, Inhalation/pharmacology , Antibody Formation/drug effects , Halothane/pharmacology , Immunologic Memory/drug effects , Isoflurane/pharmacology , Animals , Antibody-Producing Cells , Cell Count , Erythrocytes/immunology , Immunoglobulin G/biosynthesis , Male , Mice , Mice, Inbred Strains , Sheep , Spleen/cytologyABSTRACT
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.
Subject(s)
Anesthesia, Inhalation , Antibody Formation/drug effects , Halothane/pharmacology , Immunotherapy, Adoptive , Animals , Erythrocytes/immunology , Male , Mice , Mice, Inbred Strains , Sheep/immunologyABSTRACT
El objetivo de este trabajo fue estudiar el efecto de un anestésico volátil, halotano, sobre la respuesta inmunitaria en ratones. El halotano fue vaporizado con O2 100% y suministrado en cámara de flujo constante durante 40. El antígeno (GRC) fue inoculado antes de iniciar la anestesia. La respuesta inmunitaria se midió 5-6 días después del tratamiento, determinando en bazo el número de linfócitos productores de anticuerpos (CFP-IgM, CFP-IgG) y la capacidad fagocítica específica para el antígeno de las células del exudado peritoneal (CFA). Se encontro una disminución significativa del las CFP-IgM e IgG por efecto del halotano ya que el grupo de ratones que recibió únicamente el antigéno y O2 al 100% no discrepó de los controles. No se observaron alteraciones de las CFA por efecto del tratamiento. Las CFA de animales anestesiados, sin desafío antigénico, mostraran una alteración reversible de su capacidad funcional ya que recuperaram sus valores normales 24 horas después del tratamiento. Se postula que la inmunosupresión encontrada podría ser consecuencia de por lo menos 2 mecanismos de acción del halotano, uno de ellos debido al efecto directo de la droga liposolubre sobre las estructuras celulares y el otro a través de los productos de su biotransformación (AU)
Subject(s)
Mice , Animals , Halothane/pharmacology , Immunity, Cellular/drug effects , Antibody Formation/drug effectsABSTRACT
El objetivo de este trabajo fue estudiar el efecto de un anestésico volátil, halotano, sobre la respuesta inmunitaria en ratones. El halotano fue vaporizado con O2 100% y suministrado en cámara de flujo constante durante 40'. El antígeno (GRC) fue inoculado antes de iniciar la anestesia. La respuesta inmunitaria se midió 5-6 días después del tratamiento, determinando en bazo el número de linfócitos productores de anticuerpos (CFP-IgM, CFP-IgG) y la capacidad fagocítica específica para el antígeno de las células del exudado peritoneal (CFA). Se encontro una disminución significativa del las CFP-IgM e IgG por efecto del halotano ya que el grupo de ratones que recibió únicamente el antigéno y O2 al 100% no discrepó de los controles. No se observaron alteraciones de las CFA por efecto del tratamiento. Las CFA de animales anestesiados, sin desafío antigénico, mostraran una alteración reversible de su capacidad funcional ya que recuperaram sus valores normales 24 horas después del tratamiento. Se postula que la inmunosupresión encontrada podría ser consecuencia de por lo menos 2 mecanismos de acción del halotano, uno de ellos debido al efecto directo de la droga liposolubre sobre las estructuras celulares y el otro a través de los productos de su biotransformación
