title: The role of endothelin-1 and selected cytokines in the pathogenesis of Raynaud's phenomenon associated with systemic connective tissue diseases.
abstract: OBJECTIVE
  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.
authors.affiliation: Department and Clinic of Angiology, Hypertension and Diabetology, Medical University of Wroclaw, Wroclaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Rychlik-Golema
authors.forename: K
authors.initials: K
authors.lastname: Mastej
authors.forename: R
authors.initials: R
authors.lastname: Adamiec
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003240:Connective Tissue Diseases / Q000097:blood / Q000150:complications*; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000378:metabolism; D011928:Raynaud Disease / Q000097:blood / Q000209:etiology*; D019947:Receptors, Interleukin-6 / Q000097:blood; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D015415:Biomarkers; D016207:Cytokines; D019332:Endothelin-1; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D010978:Platelet Factor 4