Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

Cytokine. 2015 Apr;72(2):146-53. doi: 10.1016/j.cyto.2014.12.027. Epub 2015 Jan 31.

Abstract

Aim: Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.

Methods: Sixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).

Results: SLE patients were found to have significantly higher levels of IL-17 (p<0.001), IL-6 (p<0.01), IL-12 (p<0.001) and IL-10 (p<0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p<0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p<0.01), IL-6 (p<0.05), IL-17 (p<0.001), IL-23 (p<0.01) and TGF-β (p<0.5) and lower IFN-γ (p<0.001) and IL-10 (p<0.01) than those of healthy subjects.

Conclusion: Our study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.

Keywords: Cytokines; Rheumatoid arthritis; Systemic lupus erythematosus; T-regulatory cells; TH17.

MeSH terms

  • Adolescent
  • Adult
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology*
  • Cytokines / blood*
  • Cytokines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Interleukin-17 / blood
  • Interleukin-23 / blood
  • Interleukin-4 / blood
  • Interleukin-6 / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Transforming Growth Factor beta1 / blood
  • Young Adult

Substances

  • Cytokines
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma