The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

BMC Medicine

Yehuda Shoenfeld²  David P D’Cruz³  Esther G Meyron-Holtz¹  Gisele Zandman-Goddard⁴  Cristina Rosário⁵ 

[1] Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel;Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;Louise Coote Lupus Unit, Guy’s and St Thomas’ Hospital, London, England, UK;Department of Medicine C, Wolfson Medical Center, Holon, Israel;Center for Autoimmune Diseases, Sheba Medical Center (affiliated with the Tel-Aviv University), Tel-Hashomer 52621, Israel

关键词: Septic shock;    Catastrophic antiphospholipid syndrome (cAPS);    Adult onset Still’s disease (AOSD);    Macrophage activation syndrome (MAS);    Hyperferritinemia;   

Others  :  856937
DOI  :  10.1186/1741-7015-11-185

 received in 2013-03-18, accepted in 2013-07-29,  发布年份 2013

【 摘 要 】

Background

Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients.

Discussion

There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm.

Summary

Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”.

【 授权许可】

   
2013 Rosário et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Torti FM, Torti SV: Regulation of ferritin genes and protein. Blood 2002, 99:3505-3516.
• [2]Recalcati S, Invernizzi P, Arosio P, Cairo G: New functions for an iron storage protein: the role of ferritin in immunity and autoimmunity. J Autoimmun 2008, 30:84-89.
• [3]Zandman-Goddard G, Shoenfeld Y: Ferritin in autoimmune diseases. Autoimmun Rev 2007, 6:457-463.
• [4]Zandman-Goddard G, Shoenfeld Y: Hyperferritinemia in autoimmunity. Isr Med Assoc J 2008, 10:83-84.
• [5]Zandman-Goddard G, Orbach H, Agmon-Levin N, Boaz M, Amital H, Szekanecz Z, Szucs G, Rovensky J, Kiss E, Corocher N, Doria A, Stojanovich L, Ingegnoli F, Meroni PL, Rozman B, Gomez-Arbesu J, Blank M, Shoenfeld Y: Hyperferritinemia is associated with serologic antiphospholipid syndrome in SLE patients. Clin Rev Allergy Immunol 2011, 44:23-30.
• [6]Da Costa R, Szyper-Kravitz M, Szekanecz Z, Csepany T, Danko K, Shapira Y, Zandman-Goddard G, Orbach H, Agmon-Levin N, Shoenfeld Y: Ferritin and prolactin levels in multiple sclerosis. Isr Med Assoc J 2011, 13:91-95.
• [7]Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, Carvalho JF, Doria A, Shoenfeld Y: Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann NY Acad Sci 2007, 1109:385-400.
• [8]Agmon-Levin N, Rosario C, Katz BP, Zandman-Goddard G, Meroni P, Cervera R, Stojanovich L, Blank M, Pierangeli S, Praprotnik S, Meis E, Seguro L, Ruffatti A, Pengo V, Tincani A, Doria A, Shoenfeld Y: Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS). Lupus 2013. In press
• [9]Knovich MA, Storey JA, Coffman LG, Torti SV, Torti FM: Ferritin for the clinician. Blood Rev 2009, 23:95-104.
• [10]Harrison PM, Arosio P: The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1996, 1275:161-203.
• [11]Weiss G, Goossen B, Doppler W, Fuchs D, Pantopoulos K, Werner-Felmayer G, Grünewald K, Wachter H, Hentze MW: Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. EMBO J 1993, 12:3651-3657.
• [12]Drapier JC, Hirling H, Wietzerbin J, Kaldy P, Kuhn LC: Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J 1993, 12:3643-3649.
• [13]Bennett TD, Hayward KN, Farris RW, Ringold S, Wallace CA, Brogan TV: Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients. Pediatr Crit Care Med 2011, 12:e233-e236.
• [14]Castillo L, Carcillo J: Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med 2009, 10:387-392.
• [15]Garcia PC, Longhi F, Branco RG, Piva JP, Lacks D, Tasker RC: Ferritin levels in children with severe sepsis and septic shock. Acta Paediatr 2007, 96:1829-1831.
• [16]Demirkol D, Yildizdas D, Bayrakci B, Karapinar B, Kendirli T, Koroglu TF, Dursun O, Erkek N, Gedik H, Citak A, Kesici S, Karabocuoglu M, Carcillo JA, Turkish Secondary HLH/MAS Critical Care Study Group: Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment? Crit Care 2012, 16:R52.
• [17]Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV: Serum ferritin: past, present and future. Biochim Biophys Acta 2010, 1800:760-769.
• [18]Cohen LA, Gutierrez L, Weiss A, Leichtmann-Bardoogo Y, Zhang DL, Crooks DR, Sougrat R, Morgenstern A, Galy B, Hentze MW, Lazaro FJ, Rouault TA, Meyron-Holtz EG: Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010, 116:1574-1584.
• [19]Cozzi A, Corsi B, Levi S, Santambrogio P, Biasiotto G, Arosio P: Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood 2004, 103:2377-2383.
• [20]Moss D, Fargion S, Fracanzani AL, Levi S, Cappellini MD, Arosio P, Powell LW, Halliday JW: Functional roles of the ferritin receptors of human liver, hepatoma, lymphoid and erythroid cells. J Inorg Biochem 1992, 47:219-227.
• [21]Chen TT, Li L, Chung DH, Allen CD, Torti SV, Torti FM, Cyster JG, Chen CY, Brodsky FM, Niemi EC, Nakamura MC, Seaman WE, Daws MR: TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med 2005, 202:955-965.
• [22]Li JY, Paragas N, Ned RM, Qiu A, Viltard M, Leete T, Drexler IR, Chen X, Sanna-Cherchi S, Mohammed F, Williams D, Lin CS, Schmidt-Ott KM, Andrews NC, Barasch J: Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev Cell 2009, 16:35-46.
• [23]Morikawa K, Oseko F, Morikawa S: H- and L-rich ferritins suppress antibody production, but not proliferation, of human B lymphocytes in vitro. Blood 1994, 83:737-743.
• [24]Hann HW, Stahlhut MW, Lee S, London WT, Hann RS: Effects of isoferritins on human granulocytes. Cancer 1989, 63:2492-2496.
• [25]Broxmeyer HE, Bognacki J, Dorner MH, de Sousa M: Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages. J Exp Med 1981, 153:1426-1444.
• [26]Moroz C, Grunspan A, Zahalka MA, Traub L, Kodman Y, Yaniv I: Treatment of human bone marrow with recombinant placenta immunoregulator ferritin results in myelopoiesis and T-cell suppression through modulation of the cytokine-chemokine networks. Exp Hematol 2006, 34:159-166.
• [27]Wigginton JM: Reversal of ferritin-mediated immunosuppression by levamisole: a rationale for its application to management of the acquired immune deficiency syndrome (AIDS). Med Hypotheses 1995, 44:85-88.
• [28]Gray CP, Franco AV, Arosio P, Hersey P: Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production. Int J Cancer 2001, 92:843-850.
• [29]Li R, Luo C, Mines M, Zhang J, Fan GH: Chemokine CXCL12 induces binding of ferritin heavy chain to the chemokine receptor CXCR4, alters CXCR4 signaling, and induces phosphorylation and nuclear translocation of ferritin heavy chain. J Biol Chem 2006, 281:37616-37627.
• [30]Ruddell RG, Hoang-Le D, Barwood JM, Rutherford PS, Piva TJ, Watters DJ, Santambrogio P, Arosio P, Ramm GA: Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology 2009, 49:887-900.
• [31]Mewar D, Moore DJ, Young-Min S, Bertolaccini ML, Khamashta MA, Watson PF, Wilson AG: Antiferritin antibodies discovered by phage display expression cloning are associated with radiographic damage in rheumatoid arthritis. Arthritis Rheum 2005, 52:3868-3872.
• [32]Baerlecken NT, Linnemann A, Gross WL, Moosig F, Vazquez-Rodriguez TR, Gonzalez-Gay MA, Martin J, Kötter I, Henes JC, Melchers I, Vaith P, Schmidt RE, Witte T: Association of ferritin autoantibodies with giant cell arteritis/polymyalgia rheumatica. Ann Rheum Dis 2012, 71:943-947.
• [33]Baerlecken NT, Grobe K, Moosing F, Gross WL, Schmidt RE, Wittw T: High frequency of ferritin autoantibodies in Takayasu arteritis [abstract]. Arthritis Rheum 2012, 64:S1003.
• [34]Kuchroo VK, Umetsu DT, DeKruyff RH, Freeman GJ: The TIM gene family: emerging roles in immunity and disease. Nat Rev Immunol 2003, 3:454-462.
• [35]Meyers JH, Sabatos CA, Chakravarti S, Kuchroo VK: The TIM gene family regulates autoimmune and allergic diseases. Trends Mol Med 2005, 11:362-369.
• [36]Chakravarti S, Sabatos CA, Xiao S, Illes Z, Cha EK, Sobel RA, Zheng XX, Strom TB, Kuchroo VK: Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med 2005, 202:437-444.
• [37]Knickelbein JE, de Souza AJ, Tosti R, Narayan P, Kane LP: Cutting edge: inhibition of T cell activation by TIM-2. J Immunol 2006, 177:4966-4970.
• [38]Chong BF, Mohan C: Targeting the CXCR4/CXCL12 axis in systemic lupus erythematosus. Expert Opin Ther Targets 2009, 13:1147-1153.
• [39]Møller HJ, Moestrup SK, Weis N, Wejse C, Nielsen H, Pedersen SS, Attermann J, Nexø E, Kronborg G: Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med 2006, 34:2561-2566.
• [40]Uppal SS, Al-Mutairi M, Hayat S, Abraham M, Malaviya A: Ten years of clinical experience with adult onset Still’s disease: is the outcome improving? Clin Rheumatol 2007, 26:1055-1060.
• [41]Eisen A, Amital H: Adult still disease. In Diagnostic Criteria in Autoimmune Diseases. 1st edition. Edited by Shoenfeld Y, Cervera R, Gershwin ME. New York, NY: Humana Press; 2008:25-29.
• [42]Berkun Y, Pedeh S: Macrophage activation syndrome in juvenile idiopathic arthritis. In Diagnostic Criteria in Autoimmune Diseases. Edited by Shoenfeld Y, Cervera R, Gershwin ME. New York, NY: Humana Press; 2008:21-24.
• [43]Lian F, Wang Y, Yang X, Xu H, Liang L: Clinical features and hyperferritinemia diagnostic cutoff points for AOSD based on ROC curve: a Chinese experience. Rheumatol Int 2012, 32:189-192.
• [44]Allen CE, Yu X, Kozinetz CA, McClain KL: Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2008, 50:1227-1235.
• [45]Cinel I, Opal SM: Molecular biology of inflammation and sepsis: a primer. Crit Care Med 2009, 37:291-304.
• [46]Cervera R: Update on the diagnosis, treatment, and prognosis of the catastrophic antiphospholipid syndrome. Curr Rheumatol Rep 2010, 12:70-76.
• [47]Espinosa G, Bucciarelli S, Cervera R, Gomez-Puerta JA, Font J: Laboratory studies on pathophysiology of the catastrophic antiphospholipid syndrome. Autoimmun Rev 2006, 6:68-71.
• [48]Mavragani CP, Spyridakis EG, Koutsilieris M: Adult-onset Still’s disease: from pathophysiology to targeted therapies. Int J Inflamm 2012, 2012:879020.
• [49]Atteritano M, David A, Bagnato G, Beninati C, Frisina A, Iaria C, Bagnato G, Cascio A: Haemophagocytic syndrome in rheumatic patients. A systematic review. Eur Rev Med Pharmacol Sci 2012, 16:1414-1424.
• [50]Takahashi K, Kumakura S, Ishikura H, Murakawa Y, Yamauchi Y, Kobayashi S: Reactive hemophagocytosis in systemic lupus erythematosus. Intern Med 1998, 37:550-553.
• [51]Shimizu M, Yokoyama T, Yamada K, Kaneda H, Wada H, Wada T, Toma T, Ohta K, Kasahara Y, Yachie A: Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology (Oxford) 2010, 49:1645-1653.
• [52]Maruyama J, Inokuma S: Cytokine profiles of macrophage activation syndrome associated with rheumatic diseases. J Rheumatol 2010, 37:967-973.
• [53]Kumakura S, Ishikura H, Kondo M, Murakawa Y, Kobayashi S: Hemophagocytosis associated with MPO-ANCA positive vasculitis in systemic sclerosis. Clin Exp Rheumatol 2002, 20:411-414.
• [54]Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 2008:783-785. Erratum in: Intensive Care Med 2008, 34:783-785
• [55]Janka GE: Hemophagocytic syndromes. Blood Rev 2007, 21:245-253.
• [56]Sciascia S, Lopez-Pedrera C, Roccatello D, Cuadrado MJ: Catastrophic antiphospholipid syndrome (CAPS). Best Pract Res Clin Rheumatol 2012, 26:535-541.
• [57]Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G: HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007, 48:124-131.
• [58]Cervera R, Bucciarelli S, Plasin MA, Gomez-Puerta JA, Plaza J, Pons-Estel G, Shoenfeld Y, Ingelmo M, Espinos G, Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum On Antiphospholipid Antibodies: Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the “CAPS Registry”. J Autoimmun 2009, 32:240-245.
• [59]Kato T, Kobayashi T, Nishino H, Hidaka Y: Double-filtration plasmapheresis for resolution of corticosteroid resistant adult onset Still’s disease. Clin Rheumatol 2006, 25:579-582.
• [60]Lee SJ, Cho YN, Kim TJ, Park SC, Park DJ, Jin HM, Lee SS, Kee SJ, Kim N, Yoo DH, Park YW: Natural killer T cell deficiency in active adult-onset Still’s Disease: correlation of deficiency of natural killer T cells with dysfunction of natural killer cells. Arthritis Rheum 2012, 64:2868-2877.
• [61]Janka GE: Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007, 166:95-109.
• [62]Janka GE: Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med 2012, 63:233-246.
• [63]Schneider EM, Lorenz I, Muller-Rosenberger M, Steinbach G, Kron M, Janka-Schaub GE: Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis. Blood 2002, 100:2891-2898.
• [64]Ravelli A, Magni-Manzoni S, Pistorio A, Besana C, Foti T, Ruperto N, Viola S, Martini A: Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr 2005, 146:598-604.
• [65]Efthimiou P, Paik PK, Bielory L: Diagnosis and management of adult onset Still’s disease. Ann Rheum Dis 2006, 65:564-572.
• [66]Fujii T, Nojima T, Yasuoka H, Satoh S, Nakamura K, Kuwana M, Suwa A, Hirakata M, Mimori T: Cytokine and immunogenetic profiles in Japanese patients with adult Still’s disease. Association with chronic articular disease. Rheumatology 2001, 40:1398-1404.
• [67]Choi JH, Suh CH, Lee YM, Suh YJ, Lee SK, Kim SS, Nahm DH, Park HS: Serum cytokine profiles in patients with adult onset Still’s disease. J Rheumatol 2003, 30:2422-2427.
• [68]Priori R, Colafrancesco S, Perriconi C, Minniti A, Alessandri C, Iaiani G, Valesini G: Clinical and laboratory findings in a cohort of Italian patients with adult onset Still’s disease: the role of IL-18 as a disease biomarker [abstract]. Arthritis Rheum 2012, 64:S82.
• [69]Rau M, Schiller M, Krienke S, Heyder P, Lorenz H, Blank N: Clinical manifestations but not cytokine profiles differentiate adult-onset Still’s disease and sepsis. J Rheumatol 2010, 37:2369-2376.
• [70]Asherson RA: The catastrophic antiphospholipid (Asherson’s) syndrome in 2004 - a review. Autoimmun Rev 2005, 4:48-54.
• [71]Gogos CA, Drosou E, Bassaris HP, Skoutelis A: Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 2000, 181:176-180.
• [72]Lvovschi V, Arnaud L, Parizot C, Freund Y, Juillien G, Ghillani-Dalbin P, Bouberima M, Larsen M, Riou B, Gorochov G, Hausfater P: Cytokine profiles in sepsis have limited relevance for stratifying patients in the emergency department: a prospective observational study. PLoS One 2011, 6:e28870.
• [73]Nakakura H, Ashida A, Matsumura H, Murata T, Nagatoya K, Shibahara N, Inoue T, Tamai H: A case report of successful treatment with plasma exchange for hemophagocytic syndrome associated with severe systemic juvenile idiopathic arthritis in an infant girl. Ther Apher Dial 2009, 13:71-76.
• [74]Song KS, Sung HJ: Effect of plasma exchange on the circulating IL-6 levels in a patient with fatal hemophagocytic syndrome associated with bile ductopenia. Ther Apher Dial 2006, 10:87-89.
• [75]Matsumoto Y, Naniwa D, Banno S, Sugiura Y: The efficacy of therapeutic plasmapheresis for the treatment of fatal hemophagocytic syndrome: two case reports. Ther Apher 1998, 2:300-304.
• [76]Vignes S, Wechsler B, Amoura Z, Papo T, Francès C, Huong DL, Veyssier P, Godeau P, Piette JC: Intravenous immunoglobulin in adult Still’s disease refractory to non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol 1998, 16:295-298.
• [77]Ito T, Ozaki Y, Shimamoto K, Amuro H, Tanijiri T, Yokoi T, Son Y, Tajima K, Fukuhara S: Successful treatment with plasma exchange in adult-onset Still’s disease with hyper-IL-18-naemia and hyperallergic state. Mod Rheumatol 2008, 18:407-410.
• [78]Liu LL, Feng ML, Wang LN, Li XL, Yao L: A case report of successful treatment with plasma exchange for adult-onset Still’s disease with autoimmune hepatitis. J Clin Apher 2010, 25:74-76.
• [79]Orbach H, Katz U, Sherer Y, Shoenfeld Y: Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol 2005, 29:173-184.
• [80]Katz U, Achiron A, Sherer Y, Shoenfeld Y: Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev 2007, 6:257-259.
• [81]Uthman I, Shamseddine A, Taher A: The role of therapeutic plasma exchange in the catastrophic antiphospholipid syndrome. Transfus Apher Sci 2005, 33:11-17.
• [82]Russell JA: Management of sepsis. N Engl J Med 2006, 355:1699-1713.
• [83]Batzofin BM, Sprung CL, Weiss YG: The use of steroids in the treatment of severe sepsis and septic shock. Best Pract Res Clin Endocrinol Metab 2011, 25:735-743.
• [84]Toussaint S, Gerlach H: Immunoglobulins in adult sepsis and septic shock. Curr Infect Dis Rep 2012, 14:522-529.
• [85]Satomi A, Nagai S, Nagai T, Niikura K, Ideura T, Ogata H, Akizawa T: Effect of plasma exchange on refractory hemophagocytic syndrome complicated with myelodysplastic syndrome. Ther Apher 1999, 3:317-319.
• [86]Stegmayr BG: Apheresis as therapy for patients with severe sepsis and multiorgan dysfunction syndrome. Ther Apher 2001, 5:123-127.
• [87]Busund R, Koukline V, Utrobin U, Nedashkovsky E: Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med 2002, 28:1434-1439.
• [88]Stegmayr BG, Banga R, Berggren L, Norda R, Rydvall A, Vikerfors T: Plasma exchange as rescue therapy in multiple organ failure including acute renal failure. Crit Care Med 2003, 31:1730-1736.
• [89]Coutinho AE, Chapman KE: The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011, 335:2-13.
• [90]Rimmele T, Kellum JA: High-volume hemofiltration in the intensive care unit: a blood purification therapy. Anesthesiology 2012, 116:1377-1387.
• [91]Emmenegger U, Schaer DJ, Larroche C, Neftel KA: Haemophagocytic syndromes in adults: current concepts and challenges ahead. Swiss Med Wkly 2005, 135:299-314.
• [92]Murakami K, Suzuki C, Fujii A, Imada T: Intravenous immunoglobulin prevents release of proinflammatory cytokines in human monocytic cells stimulated with procalcitonin. Inflamm Res 2012, 61:617-622.
• [93]Emmenegger U, Frey U, Reimers A, Fux C, Semela D, Cottagnoud P, Spaeth PJ, Neftel KA: Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol 2001, 68:4-10.
• [94]Sacks S, Finn J, Sanna G, Khamashta MA, Chowdhury F, Hunt BJ, Bell R, D’Cruz DP: Adult-onset Still’s isease complicated by haemophagocytic syndrome and catastrophic antiphospholipid syndrome resulting in four limb amputation. Isr Med Assoc J 2013, 15:192-194.
• [95]Zandman-Goddard G, Shoenfeld Y: Hemophagocytic syndrome with hyperferritinemia: a stormy immunological response. Isr Med Assoc J 2013, 15:187-188.
• [96]Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N: Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006, 355:1018-1028.