Critical Imbalance of TNF-α and Soluble TNF Receptor 1 in a Patient with Macrophage Activation Syndrome: Potential Implications for Diagnostics and Treatment (original) (raw)
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Case Reports| June 06 2012
aDepartments of Oncology and Hematology and
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aDepartments of Oncology and Hematology and
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bStem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hubertus Wald Cancer Center, Hamburg, and
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aDepartments of Oncology and Hematology and
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cSection of Experimental Anesthesiology, Department of Anesthesiology, University Medical Center Ulm, Ulm, Germany
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aDepartments of Oncology and Hematology and
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Acta Haematol (2012) 128 (2): 69–72.
Received:
December 23 2011
Accepted:
February 28 2012
Published Online:
June 06 2012
Abstract
Macrophage activation syndrome (MAS) is a life-threatening disease with sustained activation of inflammatory cells and release of proinflammatory TNF-α. Under physiological conditions, TNF-α initiates a negative feedback mechanism, mediated by shedded, soluble TNF receptor ectodomains, eventually limiting the inflammatory reaction. Here, we report on a 27-year-old critically ill patient with refractory MAS and an insufficient negative feedback regulation, resulting in an overwhelming inflammatory response. A personalized treatment with soluble TNF receptor etanercept resulted in a durable remission. Further studies are warranted to establish whether the TNF cytokine profile may help to successfully guide patient selection for biological therapies.
References
Cortis E, Insalaco A: Macrophage activation syndrome in juvenile idiopathic arthritis. Acta Paediatr Suppl 2006;95:38–41.
Freeman HR, Ramanan AV: Review of haemophagocytic lymphohistiocytosis. Arch Dis Child 2011;96:688–693.
Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C: Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-γ-producing lymphocytes and IL-6- and TNF-α-producing macrophages. Blood 2005;105:1648–1651.
Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey TJ 3rd, Zentella A, Albert JD: Shock and tissue injury induced by recombinant human cachectin. Science 1986;234:470–474.
Rowlands DJ, Islam MN, Das SR, Huertas A, Quadri SK, Horiuchi K, Inamdar N, Emin MT, Lindert J, Ten VS, Bhattacharya S, Bhattacharya J: Activation of TNFR1 ectodomain shedding by mitochondrial Ca2+ determines the severity of inflammation in mouse lung microvessels. J Clin Invest 2011;121:1986–1999.
Wallach D, Engelmann H, Nophar Y, Aderka D, Kemper O, Hornik V, Holtmann H, Brakebusch C: Soluble and cell surface receptors for tumor necrosis factor. Agents Actions Suppl 1991;35:51–57.
Heaney ML, Golde DW: Soluble receptors in human disease. J Leukoc Biol 1998;64:135–146.
Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF: 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 1992;89:4845–4849.
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D: Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992;175:323–329.
Stephan JL, Zeller J, Hubert P, Herbelin C, Dayer JM, Prieur AM: Macrophage activation syndrome and rheumatic disease in childhood: a report of four new cases. Clin Exp Rheumatol 1993;11:451–456.
Makay B, Yilmaz S, Turkyilmaz Z, Unal N, Oren H, Unsal E: Etanercept for therapy-resistant macrophage activation syndrome. Pediatr Blood Cancer 2008;50:419–421.
Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL: Anti-TNF-alpha therapies: the next generation. Nat Rev Drug Discov 2003;2:736–746.
Hull KM, Drewe E, Aksentijevich I, Singh HK, Wong K, McDermott EM, Dean J, Powell RJ, Kastner DL: The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 2002;81:349–368.
Shearer WT, Reuben JM, Mullington JM, Price NJ, Lee BN, Smith EO, Szuba MP, Van Dongen HP, Dinges DF: Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol 2001;107:165–170.
Alessandri AL, Souza AL, Oliveira SC, Macedo GC, Teixeira MM, Teixeira AL: Concentrations of CXCL8, CXCL9 and sTNFR1 in plasma of patients with pulmonary tuberculosis undergoing treatment. Inflamm Res 2006;55:528–533.
Parsons PE, Matthay MA, Ware LB, Eisner MD: Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol 2005;288:L426–L431.
© 2012 S. Karger AG, Basel
2012
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