Etanercept increases tumor necrosis factor-alpha level but not sFas level in patients with rheumatoid arthritis.
BACKGROUND
Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the disease course and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.


OBJECTIVE
To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.


METHODS
We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.


RESULTS
Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P < 0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.


CONCLUSIONS
Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment.
Przemyslaw
P
Kotyla
Katarzyna
K
Jankiewicz-Ziobro
Aleksander
A
Owczarek
Eugene J
EJ
Kucharz
D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016022:Case-Control Studies; D000068800:Etanercept; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D019014:fas Receptor / Q000097:blood*
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000068800:Etanercept