Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-10T09:23:53.960Z Has data issue: false hasContentIssue false

Effects of different anaesthetic agents on immune cell function in vitro

Published online by Cambridge University Press:  28 July 2005

C. E. Schneemilch
Affiliation:
Otto-von-Guericke-University Magdeburg, Department of Anaesthesiology and Intensive Care Medicine, Magdeburg, Germany
T. Hachenberg
Affiliation:
Otto-von-Guericke-University Magdeburg, Department of Anaesthesiology and Intensive Care Medicine, Magdeburg, Germany
S. Ansorge
Affiliation:
Otto-von-Guericke-University Magdeburg, Institute of Medical Technology, Magdeburg, Germany
A. Ittenson
Affiliation:
Otto-von-Guericke-University Magdeburg, Institute of Medical Technology, Magdeburg, Germany
U. Bank
Affiliation:
Otto-von-Guericke-University Magdeburg, Institute of Immunology, Magdeburg, Germany
Get access

Extract

Summary

Background and objective: Anaesthesia may affect the regulatory balance of postoperative immune response. The aim of this study was to investigate the effects of different volatile and non-volatile anaesthetic agents and particularly of clinically used agent combinations on the proliferation capacity and cytokine production of immune cells. Methods: Peripheral blood mononuclear cells from healthy donors were PHA-activated in the presence or absence of various concentrations of thiopental, propofol, fentanyl, sufentanil, sevoflurane, nitrous oxide and combinations of these anaesthetics. Cell proliferation was assessed by tritiated thymidine uptake. Interleukin-2 production and release of the soluble IL-2 receptor were determined by enzyme immunoassays and used as measures of lymphocyte activation. Results: Thiopental inhibited cell proliferation in a dose dependent manner (P < 0.001) and reduced sIL-2R release (2090–970 pg mL−1; P < 0.05). Propofol reduced sIL-2R release at the high concentration of 10 μg mL−1 (2220 pg mL−1–1780 μg mL−1; P < 0.05). Fentanyl and sufentanil did not compensate for or enhance the inhibitory effects of thiopental. Nitrous oxide, but not sevoflurane, reduced the proliferation of human peripheral blood mononuclear cells (P < 0.05). In combinations with thiopental or nitrous oxide, sevoflurane compensated the inhibitory effects of these two agents. Fentanyl, sufentanil, sevoflurane and nitrous oxide did not affect PHA-induced IL-2 and sIL-2 receptor release by human peripheral blood mononuclear cells. Conclusion: Thiopental and nitrous oxide have immunosuppressive activity. In contrast, sevoflurane may have a beneficial effect by alleviating the immunosuppressive effects of both substances.

Type
Original Article
Copyright
© 2005 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Salo M. Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol Scand 1992; 36: 201220.Google Scholar
McBride WT, Armstrong MA, McBride SJ. Immunomodulation: an important concept in modern anaesthesia. Anaesthesia 1996; 51: 465473.Google Scholar
Correa-Sales C, Tosta CE, Rizzo LV. The effects of anesthesia with thiopental on T lymphocyte responses to antigen and mitogens in vivo and in vitro. Int J Immunopharmacol 1997; 19: 117128.Google Scholar
Hamra JG, Yaksh TL. Halothane inhibits T cell proliferation and interleukin-2 receptor expression in rats. Immunopharmacol Immunotoxicol 1996; 18: 323336.Google Scholar
Mikawa K, Akamatsu H, Nishina K et al. Propofol inhibits human neutrophil functions. Anesth Analg 1998; 87: 695700.Google Scholar
Galley HF, Webster NR. Effects of propofol and thiopentone on the immune response. Anaesthesia 1994; 52: 921923.Google Scholar
Angele MK, Faist E. Clinical review: immunodepression in the surgical patient and increased susceptibility to infections. Crit Care 2002; 6: 298305.Google Scholar
Devlin EG, Clarke RSJ, Mirakhur RK, McNeil TA. Effects of four i.v. induction agents on T-lymphocyte proliferations to PHA in vitro. Br J Anaesth 1994; 73: 315317.Google Scholar
Spiers EM, Potts RC, Simpson JR, MacConnachie A, Beck JS. Mechanisms by which barbiturates suppress lymphocyte responses to phytohaemagglutinin stimulation. Int J Pharmacol 1987; 9: 505512.Google Scholar
Devlin EG, Clarke RSJ, Mirakhur RK, McNeill TA. The effects of thiopentone and propofol on delayed hypersensitivity reactions. Anaesthesia 1995; 50: 496498.Google Scholar
Hensler T, Hecker H, Heeg K et al. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 1997; 65: 22832291.Google Scholar
Stover JF, Stocker R. Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury. Eur J Clin Pharmacol 1998; 54: 529534.Google Scholar
Eberhardt KE, Thimm BM, Spring A, Maskos WR. Dose-dependent rate of nosocomial pulmonary infection in mechanically ventilated patients with brain oedema receiving barbiturates: a prospective case study. Infection 1992; 20: 1218.Google Scholar
Briggs WA, Eustace J, Gimenez LF, Choi MJ, Scheel Jr PJ, Burdick JF. Lymphocyte suppression by glucocorticoids with cyclosporine, tacrolimus, pentoxifylline, and mycophenolic acid. J Clin Pharmacol 1999; 39: 125130.Google Scholar
Hanisch UK, Quirion R. Interleukin-2 as a neuroregulatory cytokine. Br Res Rev 1996; 21: 246284.Google Scholar
Yang KD, Liou WY, Lee CS, Chu ML, Shaio MF. Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation. J Leukoc Biol 1992; 52: 151156.Google Scholar
Loop T, Liu Z, Humar M et al. Thiopental inhibits the activation of nuclear factor kappaB. Anesthesiology 2002; 96: 12021213.Google Scholar
Le Grue SJ, Munn CG. Comparison of the immunosuppressive effects of cyclosporine, lipid-soluble anesthetics, and calmodulin antagonists. Response to exogenous interleukin 2. Transplantation 1986; 42: 679685.Google Scholar
Salo M, Pirttikangas CO, Pulkki K. Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro. Anaesthesia 1997; 52: 341344.Google Scholar
Pirttikangas CO, Perttila J, Salo M. Propofol emulsion reduces proliferative responses of lymphocytes from intensive care patients. Intens Care Med 1993; 19: 299302.Google Scholar
Galley HF, Nelson LR, Webster NR. Anaesthetic agents decrease the activity of nitric oxidase synthase from human polymorphonuclear leukocytes. Br J Anaesth 1995; 75: 326329.Google Scholar
Humar M, Pischke SE, Loop T et al. Barbiturates directly inhibit the calmodulin/calcineurin complex: a novel mechanism of inhibition of nuclear factor of activated T cells. Mol Pharmacol 2004; 65: 350361.Google Scholar
Tian J, Chau C, Hales TG, Kaufmann DL. GABA(A) receptors mediate inhibition of T cell responses. J Neuro-immunol 1999; 96: 2128.Google Scholar
McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 2001; 62: 111123.Google Scholar
Welters ID, Menzebach A, Goumon Y et al. Morphine inhibits NF-κB nuclear binding in human neutrophils and monocytes by a nitric oxide dependent mechanism. Anesthesiology 2000; 92: 16771684.Google Scholar
Bidlack JM. Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol 2000; 7: 719723.Google Scholar
Yeager MP, Procopio MA, DeLeo JA, Arruda JL, Hildebrandt L, Howell AL. Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans. Anesth Analg 2002; 94: 9499.Google Scholar
Jacobs R, Karst M, Scheinichen D et al. Effects of fentanyl on cellular immune functions in man. Int J Immunopharmacol 1999; 21: 445454.Google Scholar
Bruce DL. Halothane inhibition of RNA and protein synthesis of PHA-induced human lymphocytes. Anesthesiology 1975; 42: 1114.Google Scholar
Mitsuhata H, Shimizu R, Yokoyama MM. Suppressive effects of volatile anaesthetics on cytokine release in human peripheral blood mononuclear cells. Int J Immunopharmacol 1995; 17: 529534.Google Scholar
De Hert SG, Ten Broecke PW, Mertens E et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology 2002; 97: 4249.Google Scholar
Horn NA, de Rossi L, Robitzsch T, Hecker KE, Hutschenreuter G, Rossiant R. The effects of sevoflurane and desflurane in vitro on platelet-leukocyte adhesion in whole blood. Anaesthesia 2003; 58: 312319.Google Scholar
Matsuoka H, Kurosawa S, Horinouchi T, Kato M, Hashimoto Y. Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro. Anesthesiology 2001; 95: 14671472.Google Scholar
Loop T, Scheiermann P, Doviakue D et al. Sevoflurane inhibits phorbol–myristate–acetate-induced activator protein-1 activation in human T lymphocytes in vitro: potential role of the p38-stress kinase pathway. Anesthesiology 2004; 101: 710721.Google Scholar
Stevenson GW, Hall SC, Rudnick S, Seleny FL, Stevenson HC. The effect of anaesthetic agents on the human immune response. Anesthesiology 1990; 72: 542552.Google Scholar
Ferrero E, Ferrero ME, Marni A et al. In vitro effects of halothane on lymphocytes. Eur J Anaesthesiol 1986; 3: 321330.Google Scholar
Tschaikowsky K, Ritter J, Schröppel K, Kühn M. Volatile anesthetics differentially affect immunostimulated expression of inducible nitric oxide synthase: role of intracellular calcium. Anesthesiology 2000; 92: 10931102.Google Scholar
Nakamura K, Terasako K, Toda H et al. Mechanisms of inhibition of endothelium-dependent relaxation by halothane, isoflurane, and sevoflurane. Can J Anaesth 1994; 41: 340346.Google Scholar