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

摘要

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 1beta (IL-1beta), IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 (MIP-1alpha), MIP-1beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and total transforming growth factor-beta1 (TGF-beta1) 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-beta1 (p = 0.01) and IL-1beta (p = 0.0004) compared to controls. TGF-beta1 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-beta1 was the most consistent cytokine abnormality in patients with SLE. The associations with disease activity, lymphocyte subsets, and damage suggest that TGF-beta1 may be a therapeutic target of interest in SLE.