Th1/Th2 cytokines in patients with systemic lupus erythematosus: is tumor necrosis factor alpha protective?

Semin Arthritis Rheum. 2004 Jun;33(6):404-13. doi: 10.1016/j.semarthrit.2003.11.002.

Abstract

Objectives: To determine the circulating levels of Th1 and Th2 cytokines in patients with systemic lupus erythematosus (SLE) and to elucidate their association with disease activity and autoimmune response.

Methods: We included 52 patients and 25 healthy controls. Serum levels of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, interleukin (IL)-12p70, IL-10, and IL-4, as well as anti-DNA, -Ro, -La, -RNP, and -Sm antibodies were determined by enzyme-linked immunosorbent assay. Disease activity was recorded according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and classified as very active (SLEDAI > or = 13), moderately active (SLEDAI: 3-12), or inactive (SLEDAI < or = 2).

Results: The mean age of the patients was 34.2 +/- 12.6 years, and the mean duration of disease was 4.9 +/- 7.6 years. Twelve patients (23%), 20 patients (34.5%), and 20 patients (34.5%) had highly, moderately, and inactive SLE, respectively. Levels of IFN-gamma, TNF-alpha, and IL-12 were significantly higher in patients than in healthy controls (P <.03), as well as the IL-12/IL-10, IL-12/IL-4, IFN/IL-10, IFN/IL-4, TNF/IL-10, and TNF/IL-4 ratios (P <.01), suggesting a major participation of Th1 over Th2 cytokines. Nevertheless, a direct correlation between Th1 (IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines was observed in patients (r >.5, P <.01), indicating a mutual Th1-Th2 participation. TNF-alpha levels and the TNF/IL-10 ratio were higher in patients with inactive disease compared with patients with very active disease and controls (P <.04). IL-12 levels and IL-12/IL-4, as well as IL-12/IL-10, ratios were higher in patients with very active disease than in those with inactive SLE and controls (P <.01). IL-10 levels were associated with anti-DNA, anti-Ro, and anti-La response (P <.01).

Conclusion: Our results suggest that TNF-alpha could be a protective factor in SLE patients, whereas IL-12p70 participates in disease activity and IL-10 influences the autoimmune response (autoantibody production).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood
  • Cross-Sectional Studies
  • Cytokines / blood
  • Cytokines / immunology*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Autoantibodies
  • Cytokines
  • Tumor Necrosis Factor-alpha