Abstract
Considerable evidence has accumulated to implicate general anaesthetic agents as a cause of post-surgical immune depression. In the present study we evaluated the immuno-suppressive effects of three in vivo administered anaesthetic agents on cellular immune function in sub-human primates which did not undergo surgery. Normal rhesus monkeys received a minimal anesthetic dose of ketamine HCl, meperidine HCl, or sodium pentobarbital. Peripheral blood mononuclear cells were assayed for mitogen-induced lymphocyte proliferative responses and cell-mediated cytotoxicity (CC), including antibody-dependent CC, spontaneous CC and alloimmune CC. In vivo administration of the three agents caused significant reduction in lymphocyte functional capabilities. Within 30 min after administration of ketamine HCl or sodium pentobarbital, cytotoxic effector function was significantly depressed, with variable recovery occurring at 48 hr; cytolytic effector function was not impaired after meperidine HCl or in untreated controls. Ketamine HCl selectively suppressed effector function; mitogen-induced lymphocyte proliferative responses were not suppressed. Monkeys given meperidine HCl showed stable effector function and depressed lymphocyte proliferative function. Effects from sodium pentobarbital were non-selective, with reduced cytotoxic and proliferative lymphocyte functions. In summary, this study shows that intravenous anaesthetic agents are immunosuppressive in primates and exhibit disparate effects on afferent and efferent expressions of cellular immunity.
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- Berenbaum M. C., Fluck P. A., Hurst N. P. Depression of lymphocyte responses after surgical trauma. Br J Exp Pathol. 1973 Dec;54(6):597–607. [PMC free article] [PubMed] [Google Scholar]
- Bruce D. L. Effect of halothane anesthesia on experimental Salmonella peritonitis in mice. J Surg Res. 1967 Apr;7(4):180–185. doi: 10.1016/0022-4804(67)90048-0. [DOI] [PubMed] [Google Scholar]
- Bruce D. L., Eide K. A., Linde H. W., Eckenhoff J. E. Causes of death among anesthesiologists: a 20-year survey. Anesthesiology. 1968 May-Jun;29(3):565–569. doi: 10.1097/00000542-196805000-00039. [DOI] [PubMed] [Google Scholar]
- Bruce D. L., Wingard D. W. Anesthesia and the immune response. Anesthesiology. 1971 Mar;34(3):271–282. doi: 10.1097/00000542-197103000-00017. [DOI] [PubMed] [Google Scholar]
- Caldwell J., Notarianni L. J., Smith R. L., Fafunso M. A., French M. R., Dawson P., Bassir O. Non-human primate species as metabolic models for the human situation: comparative studies on meperidine metabolism. Toxicol Appl Pharmacol. 1979 Apr;48(2):273–278. doi: 10.1016/0041-008x(79)90033-4. [DOI] [PubMed] [Google Scholar]
- Cooper A. J., Irvine J. M., Turnbull A. R. Depression of immunological responses due to surgery. A model in the guinea-pig. Immunology. 1974 Sep;27(3):393–399. [PMC free article] [PubMed] [Google Scholar]
- Cullen B. F., Duncan P. G., Ray-Keil L. Inhibition of cell-mediated cytotoxicity by halothane and nitrous oxide. Anesthesiology. 1976 May;44(5):386–390. doi: 10.1097/00000542-197605000-00006. [DOI] [PubMed] [Google Scholar]
- Duncan P. G., Cullen B. F. Anesthesia and immunology. Anesthesiology. 1976 Nov;45(5):522–538. [PubMed] [Google Scholar]
- Duncan P. G., Cullen B. F., Pearsall N. N. Anesthesia and the modification of response to infection in mice. Anesth Analg. 1976 Nov-Dec;55(6):776–781. doi: 10.1213/00000539-197611000-00006. [DOI] [PubMed] [Google Scholar]
- Espanol T., Todd G. B., Soothill J. F. The effect of anaesthesia on the lymphocyte response to phytohaemagglutinin. Clin Exp Immunol. 1974 Sep;18(1):73–79. [PMC free article] [PubMed] [Google Scholar]
- Fauci A. S. Glucocorticoid effects on circulating human mononuclear cells. J Reticuloendothel Soc. 1979 Dec;26(Suppl):727–738. [PubMed] [Google Scholar]
- Formeister J. F., MacDermott R. P., Wickline D., Locke D., Nash G. S., Reynolds D. G., Roberson B. S. Alteration of lymphocyte function due to anesthesia: in vivo and in vitro suppression of mitogen-induced blastogenesis by sodium pentobarbital. Surgery. 1980 May;87(5):573–580. [PubMed] [Google Scholar]
- Henney C. S., Bourne H. R., Lichtenstein L. M. The role of cyclic 3',5' adenosine monophosphate in the specific cytolytic activity of lymphocytes. J Immunol. 1972 Jun;108(6):1526–1534. [PubMed] [Google Scholar]
- Humphrey L. J., Wingard D. W., Lang R. The effects of surgery and anesthesia on the immunologic responsiveness of the rat. Surgery. 1969 Jun;65(6):946–951. [PubMed] [Google Scholar]
- Jubert A. V., Lee E. T., Hersh E. M., McBride C. M. Effects of surgery, anesthesia and intraoperative blood loss on immunocompetence. J Surg Res. 1973 Dec;15(6):399–403. doi: 10.1016/0022-4804(73)90110-8. [DOI] [PubMed] [Google Scholar]
- Kanto J., Vapaavuori M., Viljanen M. K. Mitogen-induced lymphocyte transformation after general anaesthesia. Br J Anaesth. 1974 Oct;46(10):733–735. doi: 10.1093/bja/46.10.733. [DOI] [PubMed] [Google Scholar]
- Kasai M., Leclerc J. C., McVay-Boudreau L., Shen F. W., Cantor H. Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo. J Exp Med. 1979 May 1;149(5):1260–1264. doi: 10.1084/jem.149.5.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kumar S., Taylor G. Letter: Effect of surgery on lymphocytotoxicity against tumour cells. Lancet. 1974 Dec 28;2(7896):1564–1565. doi: 10.1016/s0140-6736(74)90301-8. [DOI] [PubMed] [Google Scholar]
- McCredie J. A. Antibody-dependent cellular cytotoxicity in critically ill surgical patients. Surgery. 1980 Oct;88(4):544–550. [PubMed] [Google Scholar]
- Micheels J., Degiovanni G., Castermans A. Effect of various types of anesthesia, combined with surgery, on cell mediated immunity. Acta Anaesthesiol Belg. 1978;29(2):151–163. [PubMed] [Google Scholar]
- Moudgil G. C. Proceedings: Influence of halothane on mortality from murine hepatitis virus (MHV3). Br J Anaesth. 1973 Dec;45(12):1236–1236. doi: 10.1093/bja/45.12.1236. [DOI] [PubMed] [Google Scholar]
- Moudgil G. C., Wade A. G. Anaesthesia and immunocompetence. Br J Anaesth. 1976 Jan;48(1):31–39. doi: 10.1093/bja/48.1.31. [DOI] [PubMed] [Google Scholar]
- Park S. K., Brody J. I., Wallace H. A., Blakemore W. S. Immunosuppressive effect of surgery. Lancet. 1971 Jan 9;1(7689):53–55. doi: 10.1016/s0140-6736(71)90777-x. [DOI] [PubMed] [Google Scholar]
- Penn I. Leukemias and lymphomas associated with the use of cytotoxic and immunosuppressive drugs. Recent Results Cancer Res. 1979;69:7–13. doi: 10.1007/978-3-642-81371-9_2. [DOI] [PubMed] [Google Scholar]
- Peraino C., Fry R. J., Staffeldt E. Brief communication: Enhancement of spontaneous hepatic tumorigenesis in C3H mice by dietary phenobarbital. J Natl Cancer Inst. 1973 Oct;51(4):1349–1350. doi: 10.1093/jnci/51.4.1349. [DOI] [PubMed] [Google Scholar]
- Peraino C., Fry R. J., Staffeldt E., Kisieleski W. E. Effects of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res. 1973 Nov;33(11):2701–2705. [PubMed] [Google Scholar]
- Salo M. Effect of anaesthesia and surgery on the number of and mitogen-induced transformation of T- and B-lymphocytes. Ann Clin Res. 1978 Feb;10(1):1–13. [PubMed] [Google Scholar]
- Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
- Thomas J. M., Carver M., Scott J., Williams E., Thomas F. Effect of rabbit anti-human thymocyte globulin on lymphocyte subpopulations and functions following allotransplantation in the rhesus monkey. Transplantation. 1979 Mar;27(3):163–170. doi: 10.1097/00007890-197903000-00005. [DOI] [PubMed] [Google Scholar]
- Vose B. M., Moudgil G. C. Post-operative depression of antibody-dependent lymphocyte cytotoxicity following minor surgery and anaesthesia. Immunology. 1976 Jan;30(1):123–128. [PMC free article] [PubMed] [Google Scholar]
- Whitwam J. G., Norman J. Immunology in anaesthesia and intensive care. Br J Anaesth. 1979 Jan;51(1):1–2. doi: 10.1093/bja/51.1.1. [DOI] [PubMed] [Google Scholar]
- Wilson R. D., Priano L. L., Traber D. L., Sakai H., Daniels J. C., Ritzmann S. E. An investigation of possible immunosuppression from ketamine and 100 percent oxygen in normal children. Anesth Analg. 1971 May-Jun;50(3):464–470. [PubMed] [Google Scholar]
- van den Brenk H. A., Sharpington C. Effect of phenobarbital on growth of a metastasising, allogeneic sarcoma in the rat. Experientia. 1972 Jun 15;28(6):686–688. doi: 10.1007/BF01944980. [DOI] [PubMed] [Google Scholar]