Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies

Abstract

Interleukin 1-beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was determined in knee synovium of 16 patients with rheumatoid arthritis (RA) and 16 patients with seronegative spondyloarthropathies (SSP), by using polymerase chain reaction (PCR) amplification. The pattern of cytokines observed in RA synovium is of the macrophage-fibroblast type, with the highest expression of IL-1 beta and TGF-beta. GM-CSF and IL-2 bands were visualized in a minority of patients. Neither IL-4 nor IL-5 could be detected. No significant differences were observed in the cytokine profile between patients with early (< 12 months) and more advanced disease. No differences were observed according to gender, age, rheumatoid factor status and the duration of knee synovitis. The pattern of cytokines in the synovium of SSP patients is similar to that observed in RA patients and does not change in relation to disease duration. IL-2 was the only T-cell cytokine observed. These data provide evidence that the macrophage-fibroblast cells have an important role in early and more advanced rheumatoid synovitis, and show that this is also true for SSP peripheral synovitis.

Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

“…In general the synovial compartment from relatively early RA already shows the same pattern as late RA (41). Canete et al examined the synovial tissue of patients with a disease duration shorter or longer than 12 months and were able to show that although TNF-α expression was comparable, the expression of IL-1β and IL-6 as well as of TGF-β was more characteristic of the early phases of the disease (42). More recently the synovial fluid of patients with early synovitis was examined, and the molecules that better distinguished the early synovitis (such as RA and crystal) from controls with no inflammation (OA) were IL-1β, IL-2 and IL-6, and the cytokines that better distinguished the persistent synovitis of RA from the other synovitides were IL-2, IL-13 and IL-1β (43).…”

Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: A randomized, controlled trial

“…In patients with AS, TNF concentrations are elevated in the serum (3,4) and synovial tissue (5)(6)(7). Etanercept substantially reduces disease activity in patients with spondylarthropathies, as demonstrated in a study in psoriatic arthritis (8) and a pilot study in AS (9).…”

Enhanced Expression of Integrins and CD66b on Peripheral Blood Neutrophils and Eosinophils in Patients with Rheumatoid Arthritis, and the Effect of Glucocorticoids

“…Neutrophils in synovial¯uid are capable of degrading proteoglycans and collagen in intact articular cartilage [3]. The synovial¯uid in RA also contains large quantities of immune complexes and high levels of many cytokines [4]. These cytokines are mostly produced by macrophages [4] and probably stimulate the neutrophils in synovial uid.…”

“…The synovial¯uid in RA also contains large quantities of immune complexes and high levels of many cytokines [4]. These cytokines are mostly produced by macrophages [4] and probably stimulate the neutrophils in synovial uid. In view of the large number of neutrophils in the joint cavity during active disease, this cell type probably contributes to the joint destruction in RA through the release of granule enzymes and reactive oxygen metabolites.…”