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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

INTRODUCTION: Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and...

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Autores principales: Song, Soken-Nakazawa J, Iwahashi, Mitsuhiro, Tomosugi, Naohisa, Uno, Kazuko, Yamana, Jiro, Yamana, Seizou, Isobe, Tomoyasu, Ito, Hiroki, Kawabata, Hiroshi, Yoshizaki, Kazuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978580/
https://www.ncbi.nlm.nih.gov/pubmed/24286116
http://dx.doi.org/10.1186/ar4323
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author Song, Soken-Nakazawa J
Iwahashi, Mitsuhiro
Tomosugi, Naohisa
Uno, Kazuko
Yamana, Jiro
Yamana, Seizou
Isobe, Tomoyasu
Ito, Hiroki
Kawabata, Hiroshi
Yoshizaki, Kazuyuki
author_facet Song, Soken-Nakazawa J
Iwahashi, Mitsuhiro
Tomosugi, Naohisa
Uno, Kazuko
Yamana, Jiro
Yamana, Seizou
Isobe, Tomoyasu
Ito, Hiroki
Kawabata, Hiroshi
Yoshizaki, Kazuyuki
author_sort Song, Soken-Nakazawa J
collection PubMed
description INTRODUCTION: Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients. METHODS: Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR. RESULTS: Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab. CONCLUSIONS: Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production.
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spelling pubmed-39785802014-04-09 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, Soken-Nakazawa J Iwahashi, Mitsuhiro Tomosugi, Naohisa Uno, Kazuko Yamana, Jiro Yamana, Seizou Isobe, Tomoyasu Ito, Hiroki Kawabata, Hiroshi Yoshizaki, Kazuyuki Arthritis Res Ther Research Article INTRODUCTION: Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients. METHODS: Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR. RESULTS: Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab. CONCLUSIONS: Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production. BioMed Central 2013 2013-10-02 /pmc/articles/PMC3978580/ /pubmed/24286116 http://dx.doi.org/10.1186/ar4323 Text en Copyright © 2013 Song et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Song, Soken-Nakazawa J
Iwahashi, Mitsuhiro
Tomosugi, Naohisa
Uno, Kazuko
Yamana, Jiro
Yamana, Seizou
Isobe, Tomoyasu
Ito, Hiroki
Kawabata, Hiroshi
Yoshizaki, Kazuyuki
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978580/
https://www.ncbi.nlm.nih.gov/pubmed/24286116
http://dx.doi.org/10.1186/ar4323
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