title: Anti-TNF-Mediated Modulation of Prohepcidin Improves Iron Availability in Inflammatory Bowel Disease, in an IL-6-Mediated Fashion.
abstract: Background.Anaemia is common in inflammatory bowel disease (IBD), frequently resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). ACD is characterized by macrophage iron retention induced by proinflammatory cytokines. Hepcidin is the master inducer of iron accumulation during ACD, and its production is mainly regulated by IL-6 and the novel erythroid hormone erythroferrone (ERFE). This study evaluates whether anti-TNF monoclonal antibodies therapy modurates hepcidin production and the levels of its main regulators, leading to a restoration of iron homeostasis.Methods.Sera were collected from 21 IBD patients, before each anti-TNF administration, for the first 6 weeks of therapy. Prohepcidin, erythropoietin, erythroferrone, C reactive protein, interleukin-6, iron markers, and haemoglobin levels were measured and clinical activity indexes were evaluated.Results.Serum prohepcidin, IL-6, CRP, and ferritin were significantly reduced after 6-week treatment; an increase in serum iron and total transferrin was observed. No changes in the EPO-ERFE axis were found. Remarkably, haemoglobin was significantly increased.Conclusions.Anti-TNF therapy improves iron metabolism and, subsequently, anaemia in IBD. This effect appears to be related to the modulation of the cytokine network and specifically IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD.
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Flaminia
authors.identifier: 0000-0003-3103-1398
authors.initials: F
authors.lastname: Cavallaro
authors.affiliation: Department of Clinical Sciences and Community, University of Milan, Milan, Italy; Department of Internal Medicine, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Duca
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Laura Francesca
authors.identifier: 0000-0002-9490-3723
authors.initials: LF
authors.lastname: Pisani
authors.affiliation: Laboratory Medicine Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rigolini
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Spina
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Gian Eugenio
authors.initials: GE
authors.lastname: Tontini
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Munizio
authors.affiliation: Laboratory Medicine Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
authors.forename: Elena
authors.identifier: 0000-0001-6311-7618
authors.initials: E
authors.lastname: Costa
authors.affiliation: Department of Clinical Sciences and Community, University of Milan, Milan, Italy; Department of Internal Medicine, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Maurizio
authors.identifier: 0000-0003-1558-8604
authors.initials: M
authors.lastname: Vecchi
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Luca
authors.identifier: 0000-0002-2810-9951
authors.initials: L
authors.lastname: Pastorelli
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood* / Q000150:complications / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D000069285:Infliximab / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000276:immunology*; D007501:Iron / Q000097:blood; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: C554270:EPO protein, human; C000600298:Erfe protein, human; D006454:Hemoglobins; D064451:Hepcidins; C508600:IL6 protein, human; D015850:Interleukin-6; D036361:Peptide Hormones; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D002097:C-Reactive Protein; D005293:Ferritins; D000069285:Infliximab; D007501:Iron; D000068879:Adalimumab