Analysis of serial synovial biopsies in patients with rheumatoid arthritis: description of a control group without clinical improvement after treatment with interleukin 10 or placebo.
OBJECTIVE
Analysis of serial synovial biopsy specimens is increasingly used as an outcome measure for the evaluation of therapeutic interventions. However, observations in placebo treated groups are scarce. We describe the immunohistologic features of the synovium in placebo treated patients with RA and in those who received interleukin 10 (IL-10).


METHODS
Ten patients with active RA received dosages of either placebo (n = 7) or 5 microg/kg (n = 1) or 10 microg/kg (n = 2) of recombinant human IL-10 (rhIL-10; SCH 52000, Schering-Plough, Kenilworth, NJ, USA) daily for 28 consecutive days. Synovial biopsy specimens from the knee joint were obtained by needle arthroscopy before and 4 weeks after initiation of treatment. Immunohistochemistry was performed using monoclonal antibodies specific for the following surface markers and cytokines: CD3, CD4, CD8, CD38, CD68, CD55, IL-1beta, IL-6, and tumor necrosis factor-alpha.


RESULTS
No patient exhibited clinical improvement after treatment with placebo or any rhIL-10 dosage. Microscopic analysis of synovial tissue revealed no significant change in the scores for infiltration by inflammatory cells or in the scores for the expression of cytokines after treatment.


CONCLUSIONS
Studies of serial synovial biopsies from patients treated with placebo or IL-10 revealed no changes in immunohistologic scores. This suggests that the biopsy procedure itself has no effect on the features of the synovium.
Smeets
T J
TJ
Department of Rheumatology, Leiden University Medical Center, The Netherlands.
Kraan
M C
MC
Versendaal
J
J
Breedveld
F C
FC
Tak
P P
PP
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010919:Placebos / Q000494:pharmacology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; D016207:Cytokines; D010919:Placebos; D011994:Recombinant Proteins; D016753:Interleukin-10