Rheumatology, Vol 38, 202-213, Copyright © 1999 by British Society for Rheumatology
G Steiner, M Tohidast-Akrad, G Witzmann, M Vesely, A Studnicka-Benke, A Gal, M Kunaver, P Zenz and JS Smolen
OBJECTIVE: To investigate the production of cytokines by T cells in
patients with rheumatoid arthritis (RA), reactive arthritis (REA) and
osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4,
interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF- beta),
as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by
immunoassays in sera and synovial fluid (SF) from patients with RA, REA and
OA. In addition, cytokine expression was studied by immunohistochemistry in
synovial membrane tissue sections from patients with RA and OA. RESULTS:
Almost 60% of RA sera contained at least one of the cytokines investigated,
though in low concentrations, whereas cytokines were generally not
detectable in sera from REA and OA patients. In contrast, cytokines were
found in virtually all SF; thus, the majority of SF from RA patients
contained IFN-gamma (median level 17 pg/ml) in addition to the monokines
IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not
TNF-alpha) were also frequently measured in SF from REA patients, whereas
OA samples typically contained only IL-6. Immunohistochemical analysis of
tissue sections from RA patients revealed lymphokine expression in 0.1-0.3%
of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also
IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T
cells was also observed. The majority of cytokine-expressing T cells were
CD4-positive T-helper cells typically found in perivascular areas, whereas
cytokine-producing CD8-positive T cells were found distributed throughout
the synovium. As expected, in specimens from OA patients, T cells were much
less abundant and expression of cytokines could not be detected.
CONCLUSION: These data clearly demonstrate production of cytokines by T
cells in RA synovial tissue, indicating that activated T cells play a role
in the pathophysiological events of RA.
ORIGINAL PAPERS
Cytokine production by synovial T cells in rheumatoid arthritis
Division of Rheumatology, University of Vienna, Ludwig Boltzmann- Institute of Rheumatology, Austria.
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