Glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients

Rheumatology (Oxford). 2011 Oct;50(10):1794-801. doi: 10.1093/rheumatology/ker227. Epub 2011 Jul 12.


Objective: To investigate the relative amounts of Th17 and Th1 cells present in SLE patients and the possible effects of treatments or disease features on these populations.

Methods: Peripheral blood mononuclear cells were collected from 75 SLE patients and 19 healthy controls and the proportion of Th17 and Th1 populations were assessed by flow cytometry measuring the amount of IL-17 and IFN-γ-producing cells. Gene expression of signal transducers and activators of transcription 3 (STAT3), STAT4, IL-6R and IL-12R were determined in 30 patients and 8 healthy individuals by real-time RT-PCR. Data were related to clinical and immunological parameters and to the treatment followed during the past 3 months.

Results: Th17 cells and the Th17/Th1 ratio were significantly increased in SLE patients treated with glucocorticoids compared with healthy individuals, untreated patients or those under other treatments. No association was detected with clinical parameters, but patients with anti-ENA antibodies also displayed increased Th17 responses. Disease activity (SLEDAI) is associated with the Th17/Th1 index only in glucocorticoid-treated patients. In line with these results, gene expression of STAT3 and IL-6R was up-regulated in patients taking these drugs. Accordingly, we found a positive correlation between the Th17/Th1 ratio and STAT3 levels.

Conclusions: The present work provides the first evidence that aberrant Th17/Th1 balance in SLE is linked to the use of glucocorticoids and suggests that the up-regulatory effect of these drugs on the Th17 population could be associated with their ability to increase STAT3 and IL-6R expression. Additionally, anti-ENA positivity could represent a potential biomarker for Th17 bias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / adverse effects*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Ionophores / pharmacology
  • Leukocyte Count
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Male
  • STAT3 Transcription Factor / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / drug effects*
  • Th1 Cells / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / metabolism


  • Glucocorticoids
  • Immunosuppressive Agents
  • Interleukin-17
  • Ionophores
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate