Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease.

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn's disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

Shu W ，Pang Z ，Xu C ，Lin J ，Li G ，Wu W ，Sun S ，Li J ，Li X ，Liu Z ... -  《-》

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

Cavallaro F ，Duca L ，Pisani LF ，Rigolini R ，Spina L ，Tontini GE ，Munizio N ，Costa E ，Cappellini MD ，Vecchi M ，Pastorelli L ... -  《-》

Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients.

Song SN ，Iwahashi M ，Tomosugi N ，Uno K ，Yamana J ，Yamana S ，Isobe T ，Ito H ，Kawabata H ，Yoshizaki K ... -  《-》

Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease.

Anemia is a frequent complication of inflammatory bowel disease (IBD). Hepcidin, a key mediator in this anemia, is up-regulated by high iron levels and inflammation, and serum levels are elevated in IBD. However, the extent of inflammatory activity and iron deficiency for the regulation of hepcidin is not known. This study aimed to evaluate serum hepcidin levels in anemic and non-anemic IBD patients, with iron or non-iron deficiency, and active or inactive disease. This retrospective, observational study analyzed serum hepcidin levels from 247 patients with IBD (130 Crohn's patients and 117 with ulcerative colitis) recruited at Swiss Inflammatory Bowel Disease Cohort Study centers. Patients were divided into 5 different groups using criteria of active and inactive diseases (C-reactive protein, and CDAI/MTWAI=disease activity-index), anemia (hemoglobin) and iron deficiency (ferritin) and compared to healthy controls with no signs of anemia and normal ferritin levels. Hepcidin was measured using enzyme-linked immunosorbent assay. Independent of inflammatory activity, all patients with decreased ferritin (<30μg/L) had significantly lower hepcidin levels when compared to patients and healthy controls having normal ferritin (>30μg/L). A significant correlation between serum ferritin levels and serum hepcidin was found (Spearman's Rho=0.491; p<0.001). A backward multi-linear stepwise regression analysis showed that only ferritin, and none of the inflammatory markers or age and sex correlated significantly (p=0.005) with hepcidin. This retrospective analysis suggests that iron deficiency is the key trigger for hepcidin regulation in IBD patients with anemia.

Mecklenburg I ，Reznik D ，Fasler-Kan E ，Drewe J ，Beglinger C ，Hruz P ，Swiss IBD Cohort Study Group ... -  《-》

IL-25 downregulates Th1/Th17 immune response in an IL-10-dependent manner in inflammatory bowel disease.

Su J ，Chen T ，Ji XY ，Liu C ，Yadav PK ，Wu R ，Yang P ，Liu Z ... -  《-》