Abstract
Over the last decade, numerous basic biological as well as experimental and clinical studies have firmly established the significance of tumor necrosis factor (TNF) as a principal proximal mediator of sepsis (1–4). One of the major insights that has emerged during recent years has been that under physiological circumstances, TNF activity is tightly controlled and locally restricted. In this respect, the soluble TNF receptors (sTNF-Rs) have been recognized to exert an important regulatory control on the biological actions of TNF, not only in the normal host defense against infection, but also in systemic inflammatory disorders that are related to infectious as well as noninfectious etiologies. Moreover, elevated systemic levels of sTNF-R have been demonstrated to have accurate diagnostic as well as prognostic significance in clinical sepsis and other critical illnesses (5–13). Therefore, accurate determination of sTNF-R in plasma or serum has become an important tool to gain information about a variety of pathological conditions that are characterized by TNF-mediated immune activation, both in the experimental and in the clinical setting.
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References
Bemelmans, M. H. A., Van Tits, L. J. H., and Buurman, W. A. (1996) Tumor necrosis factor: function, release and clearance. Crit. Rev. Immunol. 16, 1–11.
Strieter, R. M., Kunkel, S. L., and Bone, R. C. (1993) Role of tumor necrosis factor-α in disease states and inflammation. Crit. Care Med. 21, S447–S463.
Tracey, K. J. and Cerami, A. (1993) Tumor necrosis factor: an updated review of its biology. Crit. Care Med. 21, S415–S422.
Beutler, B. and Grau, G. E. (1993) Tumor necrosis factor in the pathogenesis of infectious diseases. Crit. Care Med. 21, S423–S435.
Girardin, E., Roux-Lombard, P., Grau, G. E., Suter, P., Galati, H., and Dayer, J. M. (1992) Imbalance between tumour necrosis factor-a and soluble TNF receptor concentrations in severe meningococcocaemia. Immunology 76, 20–23.
Cinat, M. E., Waxman, K., Granger, G. A., Pearce, W., Annas, C., and Daughters, K. (1994) Trauma causes sustained elevation of soluble tumor necrosis factor receptors. J. Am. Coll. Surg. 179, 529–537.
Rogy, M. A., Coyle, S. M., Oldenburg, H. S., Rock, C. S., Barie, P. S., Van Zee, K. J., Smith, C. G., Moldawer, L. L., and Lowry, S. F. (1994) Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients. J. Am. Coll. Surg. 178, 132–138.
Kaufmann, P., Tilz, G. P., Lueger, A., and Demel, U. (1997) Elevated plasma levels of soluble tumor necrosis factor receptor (sTNFRp60) reflect severity of acute pancreatitis. Intensive Care Med. 23, 841–848.
Froon, A. H. M., Bemelmans, M. H. A., Greve, J. W., Van der Linden, C. J., and Buurman, W. A. (1994) Increased plasma concentrations of soluble tumor necrosis factor receptors in sepsis syndrome: correlation with plasma creatinine values. Crit. Care Med. 22, 803–809.
Pilz, G., Fraunberger, P., Appel, R., Kreuzer, E., Werdan, K., Walli, A., and Seidel, D. (1996) Early prediction of outcome in score-identified, postcardiac surgical patients at high risk for sepsis, using soluble tumor necrosis factor receptor-p55 concentrations. Crit. Care Med. 24, 596–600.
Van Deuren, M., Van der Ven-Jongekrijg, J., Demacker, P. M. N., Burtelink, A. K. M., Van Dalen, R., Sauerwein, R. W., Gallati, H., Vannice, J. L., and Vander Meer, J. M. M. (1994) Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections. J. Infect. Dis. 169, 157–161.
De Beaux, A. C., Goldie, A. S., Ross, J. A., Carter, D. C., and Fearon, K. C. (1996) Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br. J. Surg. 83, 349–353.
Maessen, J. G., Fransen, E. J., Dentener, M. A., Gorgels, A. P. M., and Buurman, W. A. (1996) Serum soluble TNF receptor as a risk factor in patients with heart failure having cardiac surgery. J. Mol. Cell. Cardiol. 28, Abg (abstract).
Engelberts, I., Möller, A., Schoen, G. J. M., Van der Linden, C. J., and Buurman, W. A. (1991) Evaluation of measurement of human TNF in plasma by ELISA. Lymphokine Cytokine Res. 10, 69–76.
Engelberts, I., Stephens, S., Francot, G. J. M., Van der Linden, C. J., and Buurman, W. A. (1991) Evidence for different effects of soluble TNF-receptors on various TNF measurements in human biological fluids. Lancet 338, 515–516.
Porteu, F. and Nathan, C. (1990) Shedding of tumor necrosis factor receptors by activated human neutrophils. J. Exp. Med. 172, 599–607.
Lantz, M., Björnberg, F., Olsson, I., and Richter, J. (1994) Adherence of neutrophils induces release of soluble tumor necrosis factor receptor forms. J. Immunol. 152, 1362–1369.
Van der Poll, T., Jansen, J., Van Leenen, D., Von der Möhlen, M., Levi, M., Ten Cate, H., Gallati, H., Ten Cate, J. W., and Van Deventer, S. J. (1993) Release of soluble receptors for tumor necrosis factor in clinical sepsis and experimental endotoxemia. J. Infect. Dis. 168, 955–960.
Olszyna, D. P., Prins, J. M., Buis, B., Van Deventer, S. J., Speelman, P., and Van der Poll, T. (1998) Levels of inhibitors of tumor necrosis factor alpha and interleukin 1beta in urine and sera of patients with urosepsis. Infect. Immun. 66, 3527–3534.
Mwatha, J. K., Kimani, G., Kamau, T., Mbugua, G. G., Ouma, J. H., Mumo, J., Fulford, A. J., Jones, F. M., Butterworth, A. E., Roberts, M. B., and Dunne, D. W. (1998) High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni. J. Immunol. 160, 1992–1999.
Bethell, D. B., Flobbe, K., Cao, X. T., Day, N. P., Pham, T. P., Buurman, W. A., Cardosa, M. J., White, N. J., and Kwiatkowski, D. (1998) Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. J. Infect. Dis. 177, 778–782.
Godfried, M. H., Romijn, J. A., Van der Poll, T., Weverling, G. J., Corssmit, E. P., Endert, E., Eeftinck-Schattenkerk, J. K., and Sauerwein, H. P. (1995) Soluble receptors for tumor necrosis factor are markers for clinical course but not for major metabolic changes in human immunodeficiency virus infection. Metabolism 44, 1564–1569.
Hober, D., Benyoucef, S., Delannoy, A. S., De Groote, D., Ajana, F., Mouton, Y., and Wattre, P. (1996) Plasma levels of sTNFR p75 and IL-8 in patients with HIV-1 infection. Immunol. Lett. 52, 57–60.
Stein, D. S., Lyles, R. H., Graham, N. M., Tassoni, C. J., Margolick, J. B., Phair, J. P., Rinaldo, C., Detels, R., Saah, A., and Bilello, J. (1997) Predicting clinical progression or death in subjects with early-stage human immunodeficiency virus (HIV) infection: a comparative analysis of quantification of HIV RNA, soluble tumor necrosis factor type II receptors, neopterin, and beta2-microglobulin. Multicenter AIDS Cohort Study. J. Infect. Dis. 176, 1161–1167.
Aderka, D., Engelmann, H., Hornik, V., Skornick, Y., Levo, Y., Wallach, D., and Kushtai, G. (1991) Increased serum levels of soluble receptors for tumor necrosis factor in cancer patients. Cancer Res. 51, 5602–5607.
Gadducci, A., Ferdeghini, M., Fanucchi, A., Annicchiarico, C., Prato, B., Prontera, C., Facchini, V., and Genazzani, A. R. (1996) Serum levels of soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) in endometrial cancer. Anticancer Res. 16, 3125–3128.
Staal-Van den Brekel, A. J., Dentener, M. A., Drent, M., Ten Velde, G. P., Buurman, W. A., and Wouters, E. F. (1998) The enhanced inflammatory response in non-small cell lung carcinoma is not reflected in the alveolar compartment. Respir. Med. 92, 76–83.
Elneihoum, A. M., Falke, P., Hedblad, B., Lindgarde, F., and Ohlsson, K. (1997) Leukocyte activation in atherosclerosis: correlation with risk factors. Atherosclerosis 131, 79–84.
Elneihoum, A. M., Falke, P., Axelsson, L., Lundberg, E., Lindgarde, F., and Ohlsson, K. (1996) Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke 27, 1734–1738.
Anker, S. D., Clark, A. L., Kemp, M., Salsbury, C., Teixeira, M. M., Hellewell, P. G., and Coats, A. J. (1997) Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J. Am. Coll. Cardiol. 30, 997–1001.
Tan, L. R., Waxman, K., Scanell, G., Loli, G., and Granger, G. A. (1993) Trauma causes early release of soluble receptors for tumor necrosis factor. J. Trauma 34, 634–638.
Suttmann, U., Ockenga, J., Schneider, H., Selberg, O., Schlesinger, A., Gallati, H., Wolfram, G., Deicher, H., and Muller, M. J. (1996) Weight gain and increased concentrations of receptor proteins for tumor necrosis factor after patients with symptomatic HIV infection received fortified nutrition support. J. Am. Diet. Assoc. 96, 565–569.
Staal-Van den Brekel, A. J., Schols, A. M., Dentener, M. A., Ten Velde, G. P., Buurman, W. A., and Wouters, E. F. (1997) Metabolism in patients with small cell lung carcinoma compared with patients with non-small cell lung carcinoma and healthy controls. Thorax 52, 338–341.
Schols, A. M., Buurman, W. A., Staal-Van den Brekel, A. J., Dentener, M. A., and Wouters, E. F. (1996) Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 51, 819–824.
Staal-Van den Brekel, A. J., Schols, A. M., Dentener, M. A., Ten Velde, G. P., Buurman, W. A., and Wouters, E. F. (1997) The effects of treatment with chemotherapy on energy metabolism and inflammatory mediators in small-cell lung carcinoma. Br. J. Cancer 76, 1630–1635.
Staal-Van den Brekel, A. J., Dentener, M. A., Schols, A. M., Buurman, W. A., and Wouters, E. F. (1995) Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J. Clin. Oncol. 13, 2600–2605.
Aderka, D., Engelmann, H., Maor, Y., Brakebusch, C., and Wallach, D. (1992) Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J. Exp. Med. 175, 323–329.
Bazzoni, F. and Beutler, B. (1996) The tumor necrosis factor ligand and receptor families. N. Eng. J. Med. 334, 1717–1725.
Van Zee, K. J., Kohno, T., Fischer, E., Rock, C. S., Moldawer, L., and Lowry, S. F. (1992) Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor-alpha in vitro and in vivo. Proc. Natl. Acad. Sci. USA 89, 4845–4849.
Bemelmans, M. H. A., Gouma, D. J., and Buurman, W. A. (1994) Tissue distribution and clearance of soluble murine TNF receptors in mice. Cytokine 6, 608–615.
Bemelmans, M. H. A., Gouma, D. J., and Buurman, W. A. (1993) Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J. Immunol. 150, 2007–2017.
Peetre, C., Thysell, H., Grubb, A., and Olsson, I. (1988) A tumor necrosis factor binding protein is present in human biological fluids. Eur. J. Haematol. 41, 414–419.
Brockhaus, M., Bar-Khayim, Y., Gurwicz, S., Frensdorff, A., and Haran, N. (1992) Plasma tumor necrosis factor soluble receptors in chronic renal failure. Kidney Int. 42, 663–667.
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Bouma, M.G., Buurman, W.A. (2000). Assay of Soluble Tumor Necrosis Factor Receptors. In: Evans, T.J. (eds) Septic Shock Methods and Protocols. Methods in Molecular Medicine™, vol 36. Humana Press. https://doi.org/10.1385/1-59259-216-3:91
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DOI: https://doi.org/10.1385/1-59259-216-3:91
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