Document Detail


Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients.
MedLine Citation:
PMID:  23379428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new paradigm has emerged relating the pathogenesis of rheumatoid arthritis (RA), focused on the balance between T helper type 17 cells and regulatory T cells (T(regs) ). In humans, both subpopulations depend on transforming growth factor (TGF)-β for their induction, but in the presence of inflammatory cytokines, such as interleukin (IL)-6, the generation of Th17 is favoured. Tocilizumab is a therapeutic antibody targeting the IL-6 receptor (IL-6R), which has demonstrated encouraging results in RA. The aim of this study was to evaluate the effect of tocilizumab on Th1 cells, Th17 cells, IL-17 and interferon (IFN)-γ double secretors Th17/Th1 cells, and T(regs) in RA patients. Eight RA patients received tocilizumab monthly for 24 weeks and blood samples were obtained every 8 weeks to study T cell populations by flow cytometry. The frequency of Th17 cells, Th1 cells and Th17/Th1 cells was evaluated in peripheral blood mononuclear cells (PBMCs) activated in vitro with a polyclonal stimulus. T(regs) were identified by their expression of forkhead box protein 3 (FoxP3) and CD25 by direct staining of PBMCs. Although no changes were detected in the frequency of Th1 or Th17 cells, the percentages of peripheral T(regs) increased after therapy. In addition, the infrequent Th17/Th1 subpopulation showed a significant increment in tocilizumab-treated patients. In conclusion, tocilizumab was able to skew the balance between Th17 cells and T(regs) towards a more protective status, which may contribute to the clinical improvement observed in RA patients.
Authors:
B Pesce; L Soto; F Sabugo; P Wurmann; M Cuchacovich; M N López; P H Sotelo; M C Molina; J C Aguillón; D Catalán
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-04-02     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  237-42     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Monoclonal, Humanized / pharmacology*,  therapeutic use
Arthritis, Rheumatoid / drug therapy,  immunology*
Female
Humans
Middle Aged
Receptors, Interleukin-6 / antagonists & inhibitors*
T-Lymphocytes, Regulatory / drug effects*,  immunology*
Th1 Cells / immunology
Th17 Cells / drug effects*,  immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Receptors, Interleukin-6; 0/tocilizumab
Comments/Corrections
Comment In:
Immunotherapy. 2013 Jul;5(7):695-7   [PMID:  23829620 ]

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