Levels of Transforming Growth Factor-β Are Low in Systemic Lupus Erythematosus Patients with Active Disease

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 1 beta (IL-1 beta), IL-4, IL-6, IL- 10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein I (MIP-1 alpha), MIP-1 beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and total transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 (p = 0.01) and IL-1 beta (p = 0.0004) compared to controls. TGF-beta 1 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-beta 1 was the most consistent cytokine abnormality in patients with SLE. The associations with disease activity, lymphocyte subsets, and damage suggest that TGF-beta 1 may be a therapeutic target of interest in SLE. (First Release August 1 2010; J Rheumatol 2010;37:2039-45; doi:10.3899/jrheum.100180)