Detection of Transforming Growth Factor-beta in Rheumatoid Arthritis Synovial Tissue: Lack of Effect on Spontaneous Cytokine Production in Joint Cell Cultures

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1990 Aug 1

PMID 2201470

Citations 28

Authors

F M Brennan

D Chantry

M Turner

B Foxwell

R Maini

M Feldmann

Affiliations

Soon will be listed here.

Abstract

The presence of transforming growth factor-beta (TGF-beta) in inflammatory joint disease was investigated. Synovial fluid from patients with rheumatoid arthritis (RA) and patients with other non-autoimmune inflammatory joint diseases contained high levels of both active and latent TGF-beta. Levels of active TGF-beta did not correlate with drug regimen in either patient group or with the recovery period in the individuals with non-RA joint disease. Freshly isolated synovial cells from individuals with RA were shown by Northern blotting to express the mRNA for TGF-beta 1 and to secrete latent TGF-beta protein which could be neutralized by antibodies to TGF-beta 1 and TGF-beta 2. Lipopolysaccharide-stimulated peripheral blood mononuclear cells from normal donors produced interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) which was inhibited by pretreatment of these cells with recombinant TGF-beta. Cytokine production was not inhibited if the addition of TGF-beta was used after the inducing stimulus, suggesting that in activated cells cytokine production cannot be inhibited. This was confirmed by the observation that neither TGF-beta 1 or TGF-beta 2 inhibited spontaneous IL-1 or TNF-alpha production by rheumatoid synovial mononuclear cells in culture. These findings show that despite the presence of active TGF-beta in RA synovial joints and the spontaneous production of latent (potentially active) TGF-beta by RA cells in culture, additional TGF-beta did not inhibit ongoing cytokine synthesis in vitro. This suggests that TGF-beta may not inhibit cytokine production in the rheumatoid joint although it cannot be ruled out that in vivo TGF-beta already has an immunosuppressive effect which cannot be further increased in vitro by exogenous protein.

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