Levels of transforming growth factor-beta are low in systemic lupus erythematosus patients with active disease

J Rheumatol. 2010 Oct;37(10):2039-45. doi: 10.3899/jrheum.100180. Epub 2010 Aug 3.

Abstract

Objective: Cytokines are central regulators of the immune response but the workings of this complex network in systemic lupus erythematosus (SLE) are not fully understood. We investigated a range of inflammatory and immune-modulating cytokines to determine their value as biomarkers for disease subsets in SLE.

Methods: This was a cross-sectional study in 102 patients with SLE (87% women, disease duration 10.6 yrs). Circulating concentrations of interleukin 1β (IL-1β), IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 (MIP-1α), MIP-1β, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and total transforming growth factor-β1 (TGF-β1) were related to disease activity (SLE Disease Activity Index; SLEDAI), lymphocyte subsets, autoantibody levels, accrued damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index; SDI), and concomitant treatment.

Results: Patients with SLE had lower levels of TGF-β1 (p = 0.01) and IL-1β (p = 0.0004) compared to controls. TGF-β1 levels were lower in patients with SLEDAI scores 1-10 and SDI > 3; and were correlated with CD4+, CD8+, and natural killer cell counts; and were independent of steroid or cytotoxic drug use. Treatment with cardiovascular drugs was associated with lower IL-12 levels. No consistent disease associations existed for the other cytokines investigated.

Conclusion: Lower TGF-β1 was the most consistent cytokine abnormality in patients with SLE. The associations with disease activity, lymphocyte subsets, and damage suggest that TGF-β1 may be a therapeutic target of interest in SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interleukins / blood
  • Interleukins / immunology
  • Lupus Erythematosus, Systemic* / blood
  • Lupus Erythematosus, Systemic* / immunology
  • Lupus Erythematosus, Systemic* / physiopathology
  • Macrophage Inflammatory Proteins / blood
  • Macrophage Inflammatory Proteins / immunology
  • Middle Aged
  • Transforming Growth Factor beta / blood*
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / immunology

Substances

  • Biomarkers
  • Chemokine CCL2
  • Interleukins
  • Macrophage Inflammatory Proteins
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Interferon-gamma