{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:49:48Z","timestamp":1792507788993,"version":"4.5.0"},"reference-count":108,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM108168"],"award-info":[{"award-number":["R01GM108168"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an \u2018innocent bystander\u2019 biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.<\/jats:p>","DOI":"10.1093\/intimm\/dxx031","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T17:13:23Z","timestamp":1495559603000},"page":"401-409","source":"Crossref","is-referenced-by-count":564,"title":["Hyperferritinemia and inflammation"],"prefix":"10.1093","volume":"29","author":[{"given":"Kate F","family":"Kernan","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh 1 , 3550 Terrace Street, Pittsburgh, PA 15261 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Carcillo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh 1 , 3550 Terrace Street, Pittsburgh, PA 15261 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,25]]},"reference":[{"key":"2022093018542902500_CIT0001","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1432-1033.1987.tb11155.x","article-title":"Iron transport and storage","volume":"164","author":"Cricthon","year":"1987","journal-title":"Eur. J. Biochem"},{"key":"2022093018542902500_CIT0002","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1089\/ars.2013.5666","article-title":"Coupling heme and iron metabolism via ferritin H chain","volume":"20","author":"Gozzelino","year":"2014","journal-title":"Antioxid. Redox Signal"},{"key":"2022093018542902500_CIT0003","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1182\/blood-2009-11-253815","article-title":"Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway","volume":"116","author":"Cohen","year":"2010","journal-title":"Blood"},{"key":"2022093018542902500_CIT0004","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.exphem.2007.03.005","article-title":"Iron\/IRP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1 and ferritin during human erythroid differentiation","volume":"35","author":"Kato","year":"2007","journal-title":"Exp. Hematol"},{"key":"2022093018542902500_CIT0005","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2728(96)00022-9","article-title":"The ferritins: molecular properties, iron storage function and cellular regulation","volume":"1275","author":"Harrison","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"2022093018542902500_CIT0006","doi-asserted-by":"crossref","first-page":"30032","DOI":"10.1074\/jbc.M502951200","article-title":"The acute box cis-element in human heavy ferritin mRNA 5\u2019-untranslated region is a unique translation enhancer that binds poly\u00a9-binding proteins","volume":"280","author":"Thomson","year":"2005","journal-title":"J. Biol. Chem"},{"issue":"Pt 1","key":"2022093018542902500_CIT0007","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/bj2960175","article-title":"Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA","volume":"296","author":"Fahmy","year":"1993","journal-title":"Biochem. J"},{"key":"2022093018542902500_CIT0008","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1111\/j.1742-4658.2006.05390.x","article-title":"Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen monoxide","volume":"273","author":"Mikhael","year":"2006","journal-title":"FEBS J"},{"key":"2022093018542902500_CIT0009","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1182\/blood-2014-12-567776","article-title":"Macrophages and iron trafficking at the birth and death of red cells","volume":"125","author":"Korolnek","year":"2015","journal-title":"Blood"},{"key":"2022093018542902500_CIT0010","article-title":"A physiological model to study iron recycling in macrophages","volume":"310","author":"Delabya","year":"2005","journal-title":"Exp. Cell Res"},{"key":"2022093018542902500_CIT0011","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1096\/fasebj.3.5.2784116","article-title":"Cachectin\/tumor necrosis factor-alpha alters red blood cell kinetics and induces anemia in vivo","volume":"3","author":"Moldawer","year":"1989","journal-title":"FASEB J"},{"key":"2022093018542902500_CIT0012","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbacli.2016.03.007","article-title":"Inflammation-associated changes in lipid composition and the organization of the erythrocyte membrane","volume":"5","author":"Dinkla","year":"2016","journal-title":"BBA Clin"},{"key":"2022093018542902500_CIT0013","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1097\/01.CCM.0000079608.00875.14","article-title":"Alterations of red blood cell shape and sialic acid membrane content in septic patients","volume":"31","author":"Piagnerelli","year":"2003","journal-title":"Crit. Care Med"},{"key":"2022093018542902500_CIT0014","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/00003246-199503000-00008","article-title":"Effect of sepsis on erythrocyte intracellular calcium homeostasis","volume":"23","author":"Todd","year":"1995","journal-title":"Crit. Care Med"},{"key":"2022093018542902500_CIT0015","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1097\/CCM.0b013e3181b02b3f","article-title":"Early alterations of red blood cell rheology in critically ill patients","volume":"37","author":"Reggiori","year":"2009","journal-title":"Crit. Care Med"},{"key":"2022093018542902500_CIT0016","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00011-016-0955-9","article-title":"Red cell DAMPs and inflammation","volume":"65","author":"Mendon\u00e7a","year":"2016","journal-title":"Inflamm. Res"},{"key":"2022093018542902500_CIT0017","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1161\/01.RES.0000247067.34173.1b","article-title":"Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin","volume":"99","author":"Schaer","year":"2006","journal-title":"Circ. Res"},{"key":"2022093018542902500_CIT0018","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1073\/pnas.61.2.748","article-title":"The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase","volume":"61","author":"Tenhunen","year":"1968","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022093018542902500_CIT0019","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/jcb.21499","article-title":"Macrophages function as a ferritin iron source for cultured human erythroid precursors","volume":"103","author":"Leimberg","year":"2008","journal-title":"J. Cell. Biochem"},{"key":"2022093018542902500_CIT0020","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cmet.2005.01.003","article-title":"The iron exporter ferroportin\/Slc40a1 is essential for iron homeostasis","volume":"1","author":"Donovan","year":"2005","journal-title":"Cell Metab"},{"key":"2022093018542902500_CIT0021","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.4049\/jimmunol.1501417","article-title":"The repair of skeletal muscle requires iron recycling through macrophage ferroportin","volume":"197","author":"Corna","year":"2016","journal-title":"J. Immunol"},{"key":"2022093018542902500_CIT0022","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1182\/blood.V99.10.3505","article-title":"Regulation of ferritin genes and protein","volume":"99","author":"Torti","year":"2002","journal-title":"Blood"},{"key":"2022093018542902500_CIT0023","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2337\/dc15-0257","article-title":"Association of multiple biomarkers of iron metabolism and type 2 diabetes: The EPIC-InterAct Study","volume":"39","author":"Podmore","year":"2016","journal-title":"Diabetes Care"},{"key":"2022093018542902500_CIT0024","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.bbadis.2016.03.004","article-title":"Iron gene expression profile in atherogenic Mox macrophages","volume":"1862","author":"Marques","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"2022093018542902500_CIT0025","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ejhf.701","article-title":"Ferritin levels and risk of heart failure\u2014the Atherosclerosis Risk in Communities Study","volume":"19","author":"Silvestre","year":"2017","journal-title":"Eur. J. Heart Fail"},{"key":"2022093018542902500_CIT0026","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1089\/sur.2005.6.s1-41","article-title":"Iron and the risk of infection","volume":"6","author":"Pieracci","year":"2005","journal-title":"Surg. Infect. (Larchmt.)"},{"key":"2022093018542902500_CIT0027","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1574-6976.1993.tb00026.x","article-title":"Iron uptake mechanisms of pathogenic bacteria","volume":"12","author":"Wooldridge","year":"1993","journal-title":"FEMS Microbiol. Rev"},{"key":"2022093018542902500_CIT0028","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1128\/iai.44.2.320-325.1984","article-title":"Mechanism of impaired iron release by the reticuloendothelial system during the hypoferremic phase of experimental Neisseria meningitidis infection in mice","volume":"44","author":"Letendre","year":"1984","journal-title":"Infect. Immun"},{"key":"2022093018542902500_CIT0029","first-page":"625905","article-title":"Effect of iron\/folic Acid supplementation on the outcome of malaria episodes treated with sulfadoxine-pyrimethamine","volume":"2014","author":"Sazawal","year":"2014","journal-title":"Malar. Res. Treat"},{"key":"2022093018542902500_CIT0030","doi-asserted-by":"crossref","first-page":"554","DOI":"10.4269\/ajtmh.1993.48.554","article-title":"Etiology of hypoferremia in a recently sedentary Kalahari village","volume":"48","author":"Kent","year":"1993","journal-title":"Am. J. Trop. Med. Hyg"},{"key":"2022093018542902500_CIT0031","first-page":"319","article-title":"Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor","volume":"61","author":"Alvarez-Hern\u00e1ndez","year":"1989","journal-title":"Lab. Invest"},{"key":"2022093018542902500_CIT0032","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.3324\/haematol.2010.023879","article-title":"Polarization dictates iron handling by inflammatory and alternatively activated macrophages","volume":"95","author":"Corna","year":"2010","journal-title":"Haematologica"},{"key":"2022093018542902500_CIT0033","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/eji.200939889","article-title":"Differential regulation of iron homeostasis during human macrophage polarized activation","volume":"40","author":"Recalcati","year":"2010","journal-title":"Eur. J. Immunol"},{"key":"2022093018542902500_CIT0034","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.imbio.2008.07.010","article-title":"Effects of the Aspergillus fumigatus siderophore systems on the regulation of macrophage immune effector pathways and iron homeostasis","volume":"213","author":"Seifert","year":"2008","journal-title":"Immunobiology"},{"key":"2022093018542902500_CIT0035","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1365-2141.1981.tb07238.x","article-title":"Ferritin synthesis in inflammation. II. Mechanism of increased ferritin synthesis","volume":"49","author":"Konijn","year":"1981","journal-title":"Br. J. Haematol"},{"key":"2022093018542902500_CIT0036","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jaut.2007.11.003","article-title":"New functions for an iron storage protein: the role of ferritin in immunity and autoimmunity","volume":"30","author":"Recalcati","year":"2008","journal-title":"J. Autoimmun"},{"key":"2022093018542902500_CIT0037","doi-asserted-by":"crossref","first-page":"15285","DOI":"10.1074\/jbc.270.25.15285","article-title":"Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor-alpha","volume":"270","author":"Kwak","year":"1995","journal-title":"J. Biol. Chem"},{"key":"2022093018542902500_CIT0038","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cell.2004.10.017","article-title":"Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species","volume":"119","author":"Pham","year":"2004","journal-title":"Cell"},{"key":"2022093018542902500_CIT0039","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0006-291X(90)91466-6","article-title":"Interleukin 1 induces ferritin heavy chain in human muscle cells","volume":"169","author":"Wei","year":"1990","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2022093018542902500_CIT0040","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1093\/nar\/22.13.2678","article-title":"Translational enhancement of H-ferritin mRNA by interleukin-1 beta acts through 5\u2019 leader sequences distinct from the iron responsive element","volume":"22","author":"Rogers","year":"1994","journal-title":"Nucleic Acids Res"},{"key":"2022093018542902500_CIT0041","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1016\/j.cellsig.2014.08.018","article-title":"Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels","volume":"26","author":"Huang","year":"2014","journal-title":"Cell Signal"},{"key":"2022093018542902500_CIT0042","doi-asserted-by":"crossref","first-page":"4979","DOI":"10.1182\/blood.V90.12.4979","article-title":"Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron","volume":"90","author":"Tran","year":"1997","journal-title":"Blood"},{"key":"2022093018542902500_CIT0043","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/bj1990565","article-title":"Detection of a glycosylated subunit in human serum ferritin","volume":"199","author":"Cragg","year":"1981","journal-title":"Biochem. J"},{"key":"2022093018542902500_CIT0044","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1182\/blood-2003-09-3050","article-title":"Regulated secretion of glycosylated human ferritin from hepatocytes","volume":"103","author":"Ghosh","year":"2004","journal-title":"Blood"},{"key":"2022093018542902500_CIT0045","article-title":"Diagnostic value of and glycosylated ferritin in adult onset Still\u2019s disease","volume":"28","author":"Fautrel","year":"2001","journal-title":"J. Rheumatol"},{"key":"2022093018542902500_CIT0046","doi-asserted-by":"crossref","DOI":"10.1016\/j.berh.2008.08.006","article-title":"Adult-onset Still disease","volume":"22","author":"Fautrel","year":"2008","journal-title":"Best Pract. Res. Clin. Rheumatol"},{"key":"2022093018542902500_CIT0047","article-title":"Serum ferritin and isoferritins are tools for diagnosis of active adult Still\u2019s disease","volume":"21","author":"Van Reeth","year":"1994","journal-title":"J. Rheumatol"},{"key":"2022093018542902500_CIT0048","article-title":"Biochemical analysis of ferritin subunits in sera from adult Still\u2019s disease patients","volume":"15","author":"Higashi","journal-title":"Rheumatol Int"},{"key":"2022093018542902500_CIT0049","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/BF03044919","article-title":"Hyperferritinemia in Still syndrome in the adult and reactive hemophagocytic syndrome","volume":"92","author":"Zollner","year":"1997","journal-title":"Med. Klin. (Munich)"},{"key":"2022093018542902500_CIT0050","first-page":"1027","article-title":"High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation","volume":"30","author":"Lambotte","year":"2003","journal-title":"J. Rheumatol"},{"key":"2022093018542902500_CIT0051","first-page":"312","article-title":"The early diagnosis and clinical analysis of 57 cases of acquired hemophagocytic lymphohistiocytosis","volume":"48","author":"Wang","year":"2009","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"2022093018542902500_CIT0052","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/MD.0b013e3181a4d1a1","article-title":"Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients","volume":"88","author":"Ben m\u2019rad","year":"2009","journal-title":"Medicine (Baltimore)"},{"key":"2022093018542902500_CIT0053","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0002-9343(02)01035-5","article-title":"Drug-induced hemophagocytosis","volume":"112","author":"Lambotte","year":"2002","journal-title":"Am. J. Med"},{"key":"2022093018542902500_CIT0054","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1042\/cs0560083","article-title":"Binding of human serum ferritin to concanavalin A","volume":"56","author":"Worwood","year":"1979","journal-title":"Clin. Sci. (Lond.)"},{"key":"2022093018542902500_CIT0055","first-page":"225","article-title":"Binding of serum ferritin to concanavalin A in patients with malignancy","volume":"40","author":"Muylle","year":"1986","journal-title":"Biomed. Pharmacother"},{"key":"2022093018542902500_CIT0056","first-page":"744","article-title":"The clinical significance of glycosylated ferritin in iron overloads and hematopoietic malignancies","volume":"35","author":"Takakuwa","year":"1994","journal-title":"Rinsho Ketsueki"},{"key":"2022093018542902500_CIT0057","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/ard.59.5.347","article-title":"Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still\u2019s disease","volume":"59","author":"Vignes","year":"2000","journal-title":"Ann. Rheum. Dis"},{"key":"2022093018542902500_CIT0058","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/0192623308328544","article-title":"Ferritin expression in rat hepatocytes and Kupffer cells after lead nitrate treatment","volume":"37","author":"Fan","year":"2009","journal-title":"Toxicol. Pathol"},{"key":"2022093018542902500_CIT0059","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1523-1755.2004.00716.x","article-title":"Parenteral iron nephrotoxicity: potential mechanisms and consequences","volume":"66","author":"Zager","year":"2004","journal-title":"Kidney Int"},{"key":"2022093018542902500_CIT0060","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1164\/ajrccm.150.3.8087339","article-title":"Increased release of ferritin and iron by iron-loaded alveolar macrophages in cigarette smokers","volume":"150","author":"Wesselius","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"2022093018542902500_CIT0061","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1182\/blood-2008-05-155093","article-title":"Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism","volume":"113","author":"Ferring-Appel","year":"2009","journal-title":"Blood"},{"key":"2022093018542902500_CIT0062","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1182\/blood.V90.2.814","article-title":"Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA","volume":"90","author":"Cazzola","year":"1997","journal-title":"Blood"},{"key":"2022093018542902500_CIT0063","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s12026-014-8563-7","article-title":"sCD163 in AOSD: a biomarker for macrophage activation related to hyperferritinemia","volume":"60","author":"Colafrancesco","year":"2014","journal-title":"Immunol. Res"},{"key":"2022093018542902500_CIT0064","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1600-0609.2006.00730.x","article-title":"Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis","volume":"77","author":"Schaer","year":"2006","journal-title":"Eur. J. Haematol"},{"key":"2022093018542902500_CIT0065","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/hep.22716","article-title":"Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta\/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells","volume":"49","author":"Ruddell","year":"2009","journal-title":"Hepatology"},{"key":"2022093018542902500_CIT0066","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.0105-2896.2010.00903.x","article-title":"TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity","volume":"235","author":"Freeman","year":"2010","journal-title":"Immunol. Rev"},{"key":"2022093018542902500_CIT0067","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1182\/blood.V78.4.1056.1056","article-title":"Specific binding sites for H-ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control","volume":"78","author":"Fargion","year":"1991","journal-title":"Blood"},{"key":"2022093018542902500_CIT0068","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1182\/blood.V73.1.74.74","article-title":"Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis","volume":"73","author":"Broxmeyer","year":"1989","journal-title":"Blood"},{"key":"2022093018542902500_CIT0069","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.imbio.2013.08.011","article-title":"Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin","volume":"219","author":"Yamashita","year":"2014","journal-title":"Immunobiology"},{"key":"2022093018542902500_CIT0070","doi-asserted-by":"crossref","first-page":"37616","DOI":"10.1074\/jbc.M607266200","article-title":"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","volume":"281","author":"Li","year":"2006","journal-title":"J. Biol. Chem"},{"key":"2022093018542902500_CIT0071","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1182\/blood.V99.9.3326","article-title":"Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells","volume":"99","author":"Gray","year":"2002","journal-title":"Blood"},{"key":"2022093018542902500_CIT0072","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0008-8749(87)90293-0","article-title":"Ferritin selectively suppresses delayed-type hypersensitivity responses at induction or effector phase","volume":"109","author":"Harada","year":"1987","journal-title":"Cell. Immunol"},{"key":"2022093018542902500_CIT0073","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0306-9877(95)90075-6","article-title":"Reversal of ferritin-mediated immunosuppression by levamisole: a rationale for its application to management of the acquired immune deficiency syndrome (AIDS)","volume":"44","author":"Wigginton","year":"1995","journal-title":"Med. Hypotheses"},{"key":"2022093018542902500_CIT0074","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/PCC.0000000000001029","article-title":"A systemic inflammation mortality risk assessment contingency table for severe sepsis","volume":"18","author":"Carcillo","year":"2016","journal-title":"Pediatr. Crit. Care Med"},{"key":"2022093018542902500_CIT0075","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1111\/j.1651-2227.2007.00564.x","article-title":"Ferritin levels in children with severe sepsis and septic shock","volume":"96","author":"Garcia","year":"2007","journal-title":"Acta Paediatr"},{"key":"2022093018542902500_CIT0076","doi-asserted-by":"crossref","first-page":"e233","DOI":"10.1097\/PCC.0b013e31820abca8","article-title":"Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients","volume":"12","author":"Bennett","year":"2011","journal-title":"Pediatr. Crit. Care Med"},{"key":"2022093018542902500_CIT0077","first-page":"30032","article-title":"Cardiac dysfunction at echocardiogram and ferritin as early markers of severity in pediatric sepsis","volume":"S0021-7557","author":"Tonial","year":"2017"},{"key":"2022093018542902500_CIT0078","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/PCC.0b013e3181a1ae08","article-title":"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","volume":"10","author":"Castillo","year":"2009","journal-title":"Pediatr. Crit. Care Med"},{"key":"2022093018542902500_CIT0079","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/1741-7015-11-185","article-title":"The hyperferritinemic syndrome: macrophage activation syndrome, Still\u2019s disease, septic shock and catastrophic antiphospholipid syndrome","volume":"11","author":"Ros\u00e1rio","year":"2013","journal-title":"BMC Med"},{"key":"2022093018542902500_CIT0080","first-page":"664","article-title":"The hyperferritinemic syndrome","volume":"16","author":"Ros\u00e1rio","year":"2014","journal-title":"Isr. Med. Assoc. J"},{"key":"2022093018542902500_CIT0081","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","article-title":"How I treat hemophagocytic lymphohistiocytosis","volume":"118","author":"Jordan","year":"2011","journal-title":"Blood"},{"key":"2022093018542902500_CIT0082","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/humu.20274","article-title":"Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A","volume":"27","author":"Zur Stadt","year":"2006","journal-title":"Hum. Mutat"},{"key":"2022093018542902500_CIT0083","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.autrev.2007.11.025","article-title":"Macrophage activation syndrome in rheumatic disease: what is the role of the antigen presenting cell?","volume":"7","author":"Behrens","year":"2008","journal-title":"Autoimmun. Rev"},{"key":"2022093018542902500_CIT0084","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1365-2141.2008.07298.x","article-title":"Early diagnostic and prognostic significance of a specific Th1\/Th2 cytokine pattern in children with haemophagocytic syndrome","volume":"143","author":"Tang","year":"2008","journal-title":"Br. J. Haematol"},{"key":"2022093018542902500_CIT0085","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2141.1994.tb04905.x","article-title":"Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults","volume":"87","author":"Akashi","year":"1994","journal-title":"Br. J. Haematol"},{"key":"2022093018542902500_CIT0086","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1182\/blood.V78.11.2918.2918","article-title":"Hypercytokinemia in familial hemophagocytic lymphohistiocytosis","volume":"78","author":"Henter","year":"1991","journal-title":"Blood"},{"key":"2022093018542902500_CIT0087","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/B978-0-323-24145-8.00049-1","article-title":"Macrophage activation syndrome","volume-title":"Textbook of Pediatric Rheumatology","author":"Grom","year":"2016"},{"key":"2022093018542902500_CIT0088","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1182\/blood-2011-07-370148","article-title":"Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH","volume":"118","author":"Zhang","year":"2011","journal-title":"Blood"},{"key":"2022093018542902500_CIT0089","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jaci.2015.06.048","article-title":"Genetic predisposition to hemophagocytic lymphohistiocytosis: report on 500 patients from the Italian registry","volume":"137","author":"Cetica","year":"2016","journal-title":"J. Allergy Clin. Immunol"},{"key":"2022093018542902500_CIT0090","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/01.ccm.0000510082.89031.1e","article-title":"Genetic variants associated with hyperinflammation in septic shock","volume":"44","author":"Kernan","year":"2016","journal-title":"Crit. Care Med"},{"key":"2022093018542902500_CIT0091","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1172\/JCI43157","article-title":"Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice","volume":"121","author":"Behrens","year":"2011","journal-title":"J. Clin. Invest"},{"key":"2022093018542902500_CIT0092","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jhep.2006.07.024","article-title":"A critical role of CpG motifs in a murine peritonitis model by their binding to highly expressed toll-like receptor-9 on liver NKT cells","volume":"45","author":"Tsujimoto","year":"2006","journal-title":"J. Hepatol"},{"key":"2022093018542902500_CIT0093","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1053\/j.gastro.2010.08.020","article-title":"Type I interferons protect from Toll-like receptor 9-associated liver injury and regulate IL-1 receptor antagonist in mice","volume":"140","author":"Petrasek","year":"2011","journal-title":"Gastroenterology"},{"key":"2022093018542902500_CIT0094","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature06664","article-title":"The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response","volume":"452","author":"Muruve","year":"2008","journal-title":"Nature"},{"key":"2022093018542902500_CIT0095","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1182\/blood.V116.21.1049.1049","article-title":"Toll-like-receptor expression and cellular immune reconstitution in AML-patients with elevated serum ferritin levels after allogeneic transplant","volume":"116","author":"Elmaagacli","year":"2010","journal-title":"Blood"},{"key":"2022093018542902500_CIT0096","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/CCM.0000000000001402","article-title":"Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial","volume":"44","author":"Shakoory","year":"2016","journal-title":"Crit. Care Med"},{"key":"2022093018542902500_CIT0097","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1083\/jcb.200903124","article-title":"Glyburide inhibits the Cryopyrin\/Nalp3 inflammasome","volume":"187","author":"Lamkanfi","year":"2009","journal-title":"J. Cell Biol"},{"key":"2022093018542902500_CIT0098","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat. Med"},{"key":"2022093018542902500_CIT0099","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/MD.0000000000000022","article-title":"Hemophagocytic lymphohistiocytosis: clinical analysis of 103 adult patients","volume":"93","author":"Li","year":"2014","journal-title":"Medicine (Baltimore)"},{"key":"2022093018542902500_CIT0100","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1002\/art.38769","article-title":"Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis","volume":"66","author":"Dav\u00ec","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2022093018542902500_CIT0101","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12969-015-0055-3","article-title":"Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"13","author":"Boom","year":"2015","journal-title":"Pediatr. Rheumatol. Online J"},{"key":"2022093018542902500_CIT0102","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr. Blood Cancer"},{"key":"2022093018542902500_CIT0103","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1097\/MPH.0000000000000740","article-title":"Secondary hemophagocytic lymphohistiocytosis: do we really need chemotherapeutics for all patients?","volume":"39","author":"Haytoglu","year":"2017","journal-title":"J. Pediatr. Hematol. Oncol"},{"key":"2022093018542902500_CIT0104","doi-asserted-by":"crossref","first-page":"R52","DOI":"10.1186\/cc11256","article-title":"Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis\/sepsis\/multiple organ dysfunction syndrome\/macrophage activation syndrome: what is the treatment?","volume":"16","author":"Demirkol","year":"2012","journal-title":"Crit. Care"},{"key":"2022093018542902500_CIT0105","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clim.2009.02.005","article-title":"Macrophage activation syndrome: serological markers and treatment with anti-thymocyte globulin","volume":"132","author":"Coca","year":"2009","journal-title":"Clin. Immunol"},{"key":"2022093018542902500_CIT0106","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11940-017-0439-4","article-title":"How to treat involvement of the central nervous system in hemophagocytic lymphohistiocytosis?","volume":"19","author":"Horne","year":"2017","journal-title":"Curr. Treat. Options Neurol"},{"key":"2022093018542902500_CIT0107","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fimmu.2013.00289","article-title":"Interleukin-18 and IL-18 binding protein","volume":"4","author":"Dinarello","year":"2013","journal-title":"Front. Immunol"},{"key":"2022093018542902500_CIT0108","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.jaci.2016.10.022","article-title":"Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition","volume":"139","author":"Canna","year":"2017","journal-title":"J. Allergy Clin. Immunol"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/29\/9\/401\/46223212\/intimm_29_9_401.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/29\/9\/401\/46223212\/intimm_29_9_401.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T15:58:37Z","timestamp":1664553517000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/29\/9\/401\/3852570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,25]]},"references-count":108,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,5,25]]},"published-print":{"date-parts":[[2017,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxx031","relation":{},"ISSN":["0953-8178","1460-2377"],"issn-type":[{"value":"0953-8178","type":"print"},{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,9]]},"published":{"date-parts":[[2017,5,25]]}}}