Anti-TNF-Mediated Modulation of Prohepcidin Improves Iron Availability in Inflammatory Bowel Disease, in an IL-6-Mediated Fashion.

Laura Francesca Pisani,Roberta Rigolini,Elena Costa,Nadia Munizio,Gian Eugenio Tontini,Lorena Duca,Flaminia Cavallaro,Luisa Spina,Maria Domenica Cappellini,Maurizio Vecchi,Luca Pastorelli

doi:10.1155/2017/6843976

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.

Highlights

Anaemia is a common systemic manifestation of inflammatory bowel disease (IBD), occurring in 6% to 74% of patients [1]
Anaemia of chronic disease (ACD) is characterized by normal or increased ferritin levels, as a result of increased storage and retention of iron within the reticuloendothelial system; during chronic inflammatory diseases proinflammatory cytokines lead to the activation of Canadian Journal of Gastroenterology and Hepatology macrophages which augment their erythrophagocytic activity and express increased levels of divalent metal transporter1 (DMT-1), a transmembrane protein functioning as a major iron uptaker
C reactive protein (CRP) been suggested that anaemia is probably too common to be recognized as a complication of IBD but it should be often seen as a consistent clinical feature of it [13]

Summary

Introduction

Anaemia is a common systemic manifestation of inflammatory bowel disease (IBD), occurring in 6% to 74% of patients [1]. Anaemia of chronic disease (ACD) is characterized by normal or increased ferritin levels, as a result of increased storage and retention of iron within the reticuloendothelial system; during chronic inflammatory diseases proinflammatory cytokines lead to the activation of Canadian Journal of Gastroenterology and Hepatology macrophages which augment their erythrophagocytic activity and express increased levels of divalent metal transporter (DMT-1), a transmembrane protein functioning as a major iron uptaker. Anaemia is common in inflammatory bowel disease (IBD), frequently resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). 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 IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD

Methods

Results

Conclusion