The role of endothelin-1 and selected cytokines in the pathogenesis of Raynaud's phenomenon associated with systemic connective tissue diseases

Int Angiol. 2006 Jun;25(2):221-7.

Abstract

Aim: In the pathogenesis of Raynaud's phenomenon humoral and immunoinflammatory agents are involved. The aim of this study was the assessment of the level of endothelin-1 (ET-1), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), von Willebrand's factor (vWF) and platelet factor 4 (PF-4) in patients with Raynaud's phenomenon associated with systemic connective tissue diseases.

Methods: The examined group consisted of 32 patients (24 women and 8 men) with Raynaud's phenomenon associated with selected connective tissue diseases, aged 28-50 years. A control group consisted of 13 healthy volunteers. Immediately after a cold provocation test venous blood was taken in order to assess serum concentrations of: TNF-alpha, IL-6, IL-6sR, vWF, PF-4, antinuclear antibodies (ANA), antineutrophil antibodies (c-ANCA).

Results: In the group of patients with Raynaud's phenomenon mean serum concentration of ET-1, TNF-alpha, PF-4, and vWF was significantly greater than in the healthy group. In contrast, serum IL-6 and IL-6sR concentrations did not differ significantly between the diseased and healthy groups. In a subgroup of Raynaud's phenomenon patients showing particularly high concentration of serum ET-1 (twice as much as mean control concentration), the increase in IL-6, IL-6sR, vWF and c-ANCA concentration exhibited statistical significance in comparison with patients with lower serum ET-1 concentration. The vWF concentration exhibited positive correlation with time interval between the occurrence of clinical symptoms and serum ANA antibodies concentration. The increase in ET-1 synthesis in Raynaud's phenomenon patients is dependent on the increase in IL-6 level and c-ANCA antibodies level.

Conclusions: The patients with Raynaud's phenomenon show an increase in ET-1 and TNF-alpha concentrations. An enhanced ET-1 synthesis is dependent on the augmentation of serum c-ANCA antibodies and IL-6 concentrations.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Antibodies, Antinuclear / blood
  • Biomarkers / blood
  • Connective Tissue Diseases / blood
  • Connective Tissue Diseases / complications*
  • Cytokines / metabolism*
  • Disease Progression
  • Endothelin-1 / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Platelet Factor 4 / metabolism
  • Raynaud Disease / blood
  • Raynaud Disease / etiology*
  • Receptors, Interleukin-6 / blood
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / metabolism
  • von Willebrand Factor / metabolism

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antibodies, Antinuclear
  • Biomarkers
  • Cytokines
  • Endothelin-1
  • Interleukin-6
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha
  • von Willebrand Factor
  • Platelet Factor 4