The effect of disease activity related cytokines on the fibrinolytic potential and cICAM-1 expression in rheumatoid arthritis

• Published in: Journal of rheumatology Vol. 27; no. 11; p. 2545
• Main Authors: Kamper, E F, Kopeikina, L T, Trontzas, P, Potamianou, A, Tsiroglou, E, Stavridis, J C
• Format: Journal Article
• Language: English
• Published: Canada 01.11.2000
• Subjects: Aged; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - physiopathology; Female; Fibrinolysis; Humans; Intercellular Adhesion Molecule-1 - blood; Interleukin-10 - physiology; Interleukin-6 - physiology; Male; Middle Aged; Plasminogen Activator Inhibitor 1 - blood; Reference Values; Severity of Illness Index; Tissue Plasminogen Activator - blood; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0315-162X

We studied the relation of pro and antiinflammatory cytokines to disease activity, coagulation, and fibrinolytic variables as well as to circulating intercellular adhesive molecule- 1 (cICAM-1), so as to better understand the cascade of events implicated in the inflammatory process in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10, cICAM-1, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor- 1 (PAI-1), and D-dimer antigens were measured by ELISA in the blood of 45 RA patients and 33 healthy subjects (HS). The Stoke Index was used to describe the disease activity in patients, who were divided into subgroups: A: minimal-mild disease activity (n = 23, Stoke Index = 1-7); B: moderate disease activity (n = 12, Stoke Index = 8-11); C: severe disease activity (n = 9, Stoke Index = 12-17). TNF-alpha, IL-6, and IL-10 were significantly higher in RA patients than in HS. TNF-alpha and IL-6, in contrast to IL-10, have the tendency to increase progressively with the increase of disease activity from subgroup to subgroup, correlating significantly with Stoke Index. TNF-alpha and IL-6 correlated positively with PAI-1 and negatively with t-PA and D-dimer. Moreover, a positive correlation of IL-6 with fibrinogen and of both cytokines with PAI-1/t-PA molar ratio were found in all RA patients, while IL-10 showed a significant negative correlation only with PAI-1. Serum cICAM-1 was significantly elevated in RA compared to HS, showing a tendency to increase with the increase of disease activity from subgroup to subgroup. A positive correlation of cICAM-1 with TNF-alpha and IL-6 and a negative one with IL-10 was observed in RA. Proinflammatory cytokines TNF-alpha and IL-6 may be implicated in the imbalance of coagulation and fibrinolysis in favor of coagulation and the impairment of the adhesive molecule pathway in RA. This action of TNF-alpha and IL-6 does not seem to be countered by the antiinflammatory cytokine IL-1O action.