Tumor necrosis factor alpha blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue.
OBJECTIVE
To determine whether treatment with the chimeric anti-tumor necrosis factor alpha antibody infliximab could reduce cellularity by the induction of apoptosis in synovial tissue.


METHODS
Twenty-four rheumatoid arthritis patients with active disease were randomized to receive either infliximab (3 mg/kg) (n = 12) or placebo (n = 12) intravenously. All patients were subjected to arthroscopic synovial biopsy directly before initiation of treatment. A second arthroscopic synovial biopsy of the same index joint was performed 48 hours after the first arthroscopy. After the second arthroscopy, the patients who had initially received placebo were also treated with infliximab in an extension study. A third arthroscopy was performed in all patients on day 28. Immunohistologic analysis was performed to characterize the cell infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and electron microscopy.


RESULTS
At 48 hours after initiation of infliximab treatment, there was a significant reduction in the number of intimal macrophages; this was not observed in the placebo group. The number of sublining macrophages, T cells, and plasma cells also tended to be decreased in infliximab-treated patients, but not in the placebo group. Of interest, we did not detect any increase in the number of apoptotic cells after infliximab treatment.


CONCLUSIONS
Infliximab therapy may reduce the number of inflammatory cells in rheumatoid synovial tissue as soon as 48 hours after initiation of treatment, but apparently not by induction of apoptosis. Conceivably, decreased cell infiltration primarily results from early inhibition of cell migration.
Smeets
Tom J M
TJ
Division of Clinical Immunology and Rheumatology, F4-218 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. T.J.Smeets@amc.uva.nl
Kraan
Maarten C
MC
van Loon
Marieke E
ME
Tak
Paul-Peter
PP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D001402:B-Lymphocytes / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D008264:Macrophages / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab