title: Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells.
abstract: 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.
  
  
  CONCLUSIONS
  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: Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sikmn@mahidol.ac.th
authors: K
authors: K
authors: Maneechotesuwan
authors: K
authors: K
authors: Kasetsinsombat
authors: V
authors: V
authors: Wamanuttajinda
authors: A
authors: A
authors: Wongkajornsilp
authors: P J
authors: PJ
authors: Barnes
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase