Document Detail


Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells.
MedLine Citation:
PMID:  23331562     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Plasticity of CD4(+) lymphocyte Th17/regulatory T cell (Treg) subsets is involved in the pathogenesis of chronic airway inflammatory diseases, such as asthma. Reversal of Th17/Treg cell balance towards Treg cells may be beneficial for the suppression of chronic Th2 cell-mediated inflammatory diseases, such as asthma. However, the effect of the combination of corticosteroids and a statin on the ratio of Treg/Th17 cells is unknown.
OBJECTIVE: We investigated the in vitro effects of the combination of simvastatin and fluticasone propionate (FP) on the numbers of Treg and Th17 cells in asthmatic patients after co-incubation with monocyte-derived DCs (mDCs), and explored the underlying signalling pathways involved.
METHODS: Using flow cytometry, we determined the effects of FP and simvastatin on Treg/Th17 balance after co-incubation of asthmatic CD4(+) T cells with mDCs. We also measured the relevant Treg and Th17-polarizing cytokines released from mDCs and also investigated the role of indoleamine 2, 3-dioxygenase (IDO) in this response.
RESULTS: The combination of simvastatin and FP significantly increased Treg and concomitantly reduced Th17 cell numbers to a greater extent than FP or statin treatment alone. The enhancing effects of simvastatin on FP effects were mediated through the up-regulation of indoleamine 2, 3-dioxygenase and interleukin (IL)-10, together with down-regulation of IL-6 and IL-23 expression in mDCs.
CONCLUSION: On the basis of this in vitro model of asthma, we suggest that the combination of a statin and a corticosteroid could augment the Treg/Th17 cell ratio and thus more effectively suppress airway inflammation in asthma patients. This may be particularly relevant in the treatment of severe asthma where Th17 cells are activated and linked to neutrophilic inflammation.
Authors:
K Maneechotesuwan; K Kasetsinsombat; V Wamanuttajinda; A Wongkajornsilp; P J Barnes
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  43     ISSN:  1365-2222     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  212-22     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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