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a Department of
Medicine Unit of Rheumatology, Karolinska Hospital, Stockholm, Sweden, b Unit of Neuroimmunology, Karolinska Hospital, c Department of Orthopaedic
Surgery, University Hospital, Uppsala, Sweden, d Department
of Orthopaedics, University Hospital, Malmö, Sweden, e Department of Rheumatology, Astrid Lindgren's
Children's Hospital, Stockholm, Sweden
Correspondence to: Dr Ann-Kristin Ulfgren, Rheumatology Research Laboratory, CMM L8-004, Karolinska Hospital, S-171 76 Stockholm, Sweden E-mail: Ann-Kristin.Ulfgren{at}cmm.ki.se
Accepted for publication 10 December 1999
OBJECTIVES
Assessment
of the numbers and spatial distribution of cells producing interleukin
1
(IL1), interleukin 1
(IL1), tumour necrosis factor (TNF), and interleukin 6 (IL6) in the synovial membranes of patients
with rheumatoid arthritis (RA).
METHODSSynovial
tissue specimens from 40 patients with RA and eight patients with
non-rheumatic disease were obtained by arthroscopy guided biopsy
techniques or during joint surgery. A modified immunohistochemical method detecting cytokine producing rather than cytokine binding cells
was applied to determine cytokine synthesis in fixed cryopreserved sections. Computerised image analysis methods provided comparative quantitative assessments.
RESULTSA wide
variation between subjects was recorded for both quantities and
profiles of expressed cytokines, despite similar macroscopic and
histopathological features of inflammation. IL1 and IL1 were the
most abundant monokines identified, though produced at different sites.
IL1 was predominantly seen in vascular endothelial cells, whereas
IL1 staining was mainly shown in macrophages and fibroblasts.
Concordant results for the detection of TNF at protein and mRNA
levels were obtained with an unexpectedly low number of TNF
producing cells compared with IL1 expressing cells in many patients
with RA. Specimens acquired arthroscopically from areas with maximum
signs of macroscopic inflammation showed an increased number of TNF
producing cells in pannus tissue compared with that occurring in
synovial villi of a given joint. This clustered distribution was not
found for cells expressing any of the other studied cytokines.
CONCLUSIONThe
recorded heterogeneous profile of proinflammatory cytokine synthesis in
the synovial membrane among patients with RA may provide a clue for an
understanding of the wide variation in responsiveness to different
modes of antirheumatic treatment between patients.
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