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Inhibition of IL-6 function corrects Th17/Treg imbalance in rheumatoid arthritis patients.
MedLine Citation:
PMID:  22488116     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: From an immunological standpoint, the mechanisms by which Tocilizumab (TCZ), a humanized anti-interleukin-6 (IL-6) receptor antibody, improves Rheumatoid Arthritis (RA) patients are still not fully understood. In vitro studies and results from mouse models have emphasized the critical role of IL-6 in Th17 differentiation. Th17 lymphocytes have been demonstrated to be strongly involved in RA pathogenesis. The objective of the current study was to investigate the effect of IL-6 blockade on the Th17/Treg balance in patients with active RA. METHODS: Patients suffering from active RA for whom TCZ was indicated by their rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed and the disease activity score rated by the 28 joint count (DAS28). Serum cytokine levels and other inflammation parameters were measured before the first infusion and after 3 infusions of TCZ (8mg/Kg). RESULTS: Compared to controls, Th17 cells (CD4(+) IL-17(+) ) were increased and Treg (CD4(+) CD25(high) Foxp3(+) ) decreased in the peripheral blood of active RA patients. The suppressive function of circulating Treg was not impaired in active RA patients. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from 0.90 to 0.45%; p=0.009) and an increase in the percentage of Treg (3.05 to 3.94%; p=0.0039) in all the patients. CONCLUSION: This study reports for the first time that the inhibition of IL-6 function by TCZ restores the Th17/Treg imbalance in RA patients.
Authors:
Maxime Samson; Sylvain Audia; Nona Janikashvili; Marion Ciudad; Malika Trad; Jennifer Fraszczak; Paul Ornetti; Jean-Francis Maillefert; Pierre Miossec; Bernard Bonnotte
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Affiliation:
INSERM, UMR1098, F-25020 Besançon cedex, France; Université de Bourgogne, UMR1098, Faculté de Médecine, IFR100, F-21000 Dijon, France.
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