Abstract
Lipopolysaccharide (LPS) tolerance is characterized by an impaired proinflammatory cytokine production upon restimulation of mononuclear cells with LPS. LPS is considered the primary activator for this phenomenon. In response to major injury and extensive abdominal surgery, an immune reaction comparable to LPS tolerance has been described. Therefore, it was investigated whether primary stimuli other than LPS could induce cytokine downregulation. In eight patients who underwent a laparoscopic cholecystectomy, blood was obtained before and after induction of anaesthesia and 2, 6, and 24 hr postoperatively. Ex vivo stimulation of whole blood resulted in a transient reduction (nadir 2 hr postoperatively) of tumor necrosis factor-α, interleukin (IL)-1β, and interferon-γ release, while IL-1 receptor antagonist production increased. Stress hormones, LPS-binding protein, and bactericidal/permeability-increasing protein do not seem to be involved. This study shows that minimally invasive surgery, in the absence of endotoxemia, can induce LPS desensitization. These data suggest that prior endotoxemia is not essential for the development of LPS tolerance.
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REFERENCES
Ertel W, Kremer JP, Kenney J, Steckholzer U, Jarrar D, Trentz O, Schildberg FW: Downregulation of proinflammatory cytokine release in whole blood from septic patients. Blood 85:1341–1347, 1995
Keuter M, Dharmana E, Gasem MH, Van der Ven-Jongekrijg J, Djokomoeljanto R, Dolmans WMV, Demacker PNM, Sauerwein R, Gallati H, Van der Meer J: Patterns of proinflammatory cytokines and inhibitors during typhoid fever. J Infect Dis 169:1306–1311, 1994
Munoz C, Carlet J, Fitting C, Misset B, Bierot JP, Cavaillon JM: Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88:1747–1754, 1991
Van Deuren M, Van der Ven-Jongekrijg J, Demacker PNM, Bartelink AKM, Van Dalen R, Sauerwein R, Gallati H, Vannice JL, Van der Meer J: Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections. J Infect Dis 169:157–161, 1994
Randow F, Syrbe U, Meisel C, Krausch D, Zuckermann H, Platzer C, Volk HD: Mechanism of endotoxin desensitization: Involvement of interleukin 10 and transforming growth factor β. J Exp Med 181:1887–1892, 1995
Volk HD, Thieme M, Heym S, Döcke WD, Ruppe U, Tausch W, Manger D, Zuckermann S, Golosubow A, Nieter B, Reinke P, Seiler FR, Ax W, Baehr R: Alterations in function and phenotype of monocytes from patients with septic disease: Predictive value and new therapeutic strategies. Behring Inst Mitt 88:208–215, 1991
Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W: Monocyte deactivation in septic patients: Restoration by IFN-γ treatment. Nature Med 3:678–681, 1997
Van der Poll T, Coyle SM, Moldawer LL, Lowry SF: Changes in endotoxin-induced cytokine production by whole blood after in vivo exposure of normal humans to endotoxin. J Infect Dis 174:1356–1360, 1996
Lyons A, Kelly J, Rodrick ML, Mannick JA, Lederer JA: Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection. Ann Surg 226:450–460, 1997
O'Sullivan ST, Lederer JA, Horgan AF, Chin DHL, Mannick JA, Rodrick ML: Major injury leads to predominance of the T helper-2-lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection. Ann Surg 222:482–492, 1995
Klava A, Windsor A, Boylston AW, Reynolds JV, Ramsden CW, Guillou PJ: Monocyte activation after open and laparoscopic surgery. Br J Surg 84:1152–1156, 1997
Hensler T, Hecker H, Heeg K, Heidecke CD, Bartels H, Barthlen W, Wagner H, Siewert JR, Holzmann B: Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 65:2283–2291, 1997
Berger D, Bölke E, Seidelmann M, Vasilescu C, Beger HG: Endotoxin-induced cytokine release from whole blood: Similarities between monocyte dysfunction in septic disease and during postoperative acute phase response. J Endotoxin Res 4:17–24, 1997
Sturk A, Joop K, Ten Cate JW, Thomas LLM: Optimalization of a chromogenic assay for endotoxin in blood. In Bacterial Endotoxins: Structure, Biomedical Significance and Detection with the Limulus Amoebocyte Lysate Test, Ten Cate JW, Büller HR, Sturk A, Levin J (eds). New York, Alan R. Liss, 1985, pp 117–136
Moeniralam HS, Bemelman WA, Endert E, Koopmans R, Sauerwein HP, Romijn JA: The decrease in nonsplenic interleukin-6 (IL-6) production after splenectomy indicates the existence of a positive feedback loop of IL-6 production during endotoxemia in dogs. Infect Immun 65:2299–2305, 1997
Moeniralam HS, Endert E, Ackermans MT, Van Lanschot JJB, Sauerwein HP, Romijn JA: Sufentanil alters the inflammatory, endocrine and metabolic responses to endotoxin in dogs. Am J Physiol (in press)
Froon AHM, Dentener MA, Greve JWM, Ramsay G, Buurman WA: Lipopolysaccharide toxicity-regulating proteins in bacteremia. J Infect Dis 171:1250–1257, 1995
Dentener MA, Francot GJM, Smit FT: Presence of bactericidal/permeability-increasing protein in disease: Detection by ELISA. J Infect Dis 171:739–743, 1995
Van der Poll T, Jansen J, Endert E, Sauerwein HP, Van Deventer SJH: Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood. Infect Immun 62:2046–2050, 1994
Van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF: Epinephrine inhibits tumor necrosis factor-α and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97:713–719, 1996
Petrovsky N, Harrison LC: Diurnal rhythmicity of human cytokine production. J Immunol 158:5163–5168, 1997
Kimmings AN, Pajkrt D, Zaaijer K, Moojen TM, Meenan JK, Ten Cate JW, Van Deventer SJH: Factors involved in early in vitro endotoxin hyporesponsiveness in human endotoxemia. J Endotoxin Res 3:283–289, 1996
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Lemaire, L.C.J.M., van der Poll, T., van Lanschot, J.J.B. et al. Minimally Invasive Surgery Induces Endotoxin-Tolerance in the Absence of Detectable Endotoxemia. J Clin Immunol 18, 414–420 (1998). https://doi.org/10.1023/A:1023282706945
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DOI: https://doi.org/10.1023/A:1023282706945