The role of endothelin-1 and selected cytokines in the pathogenesis of Raynaud's phenomenon associated with systemic connective tissue diseases.
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.
Rychlik-Golema
W
W
Department and Clinic of Angiology, Hypertension and Diabetology, Medical University of Wroclaw, Wroclaw, Poland.
Mastej
K
K
Adamiec
R
R
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
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