Ef. Kamper et al., The effect of disease activity related cytokines on the fibrinolytic potential and cICAM-1 expression in rheumatoid arthritis, J RHEUMATOL, 27(11), 2000, pp. 2545-2550
Objective. We studied the relation of pro and antiinflammatory cytokines to
disease activity, coagulation, and fibrinolytic variables as well as to ci
rculating intercellular adhesive molecule-1 (cICAM-1), so as to better unde
rstand the cascade of events implicated in the inflammatory process in rheu
matoid arthritis (RA).
Methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10
, cICAM-1, tissue-type plasminogen activator (t-PA), plasminogen activator
inhibitor-1 (PAI-I), and D-dimer antigens were measured by ELISA in the blo
od 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 subgro
ups: A: minimal-mild disease activity (n = 23, Stoke Index = 1-7); B: moder
ate disease activity (n = 12, Stoke Index = 8-11); C: severe disease activi
ty (n = 9, Stoke Index = 12-17).
Results. TNF-alpha, IL-6, and IL-10 were significantly higher in RA patient
s than in HS. TNF-alpha and IL-6, in contrast to IL-10, have the tendency t
o increase progressively with the increase of disease activity from subgrou
p 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. M
oreover, a positive correlation of IL-6 with fibrinogen and of both cytokin
es with PAI-1/t-PA molar ratio were found in all RA patients, while IL-10 s
howed a significant negative correlation only with PAI-1. Serum cICAM-1 was
significantly elevated in RA compared to HS, showing a tendency to increas
e with the increase of disease activity from subgroup to subgroup. A positi
ve correlation of cICAM-1 with TNF-alpha and IL-6 and a negative one with I
L-10 was observed in RA.
Conclusion. Proinflammatory cytokines TNF-alpha and IL-6 may be implicated
in the imbalance of coagulation and fibrinolysis in favor of coagulation an
d 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 cyto
kine IL-10 action.