Interleukin‐1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid

Abstract

We examined the role of interleukin-1 (IL-1) in the chemotactic activity of rheumatoid arthritis (RA) synovial fluid (SF). Crude RA SF was found to be chemotactic for B cells and T cells. After AcA 54 gel filtration, the principal peaks of chemotactic activity were found in the 5-kd, 16-kd, and 60-kd fractions. The majlority of the chemotactic activity for both the B cells (74-85%) and the T cells (69-78%) was removed from these fractions by treatment with anti-IL-1 antibody. However, in crude SF, approximately 60% of the chemotactic activity for B cells and 40% of that for T cells, was removed, indicating the presence of additional chernotactic factors in RA SF. IL-1 activity, measured by tlhe thymocyte proliferation assay, was demonstrated in RA SF AcA 54 Ultrogel fractions after separation from inhibitors of thymocyte proliferation that are present in crude SF. On chromatofocusing of the 16-kd fraction, the principal peaks of both thymocyte proliferation activity and chemotactic activity were present in

Anchorage-independent growth of synoviocytes from arthritic and normal joints. Stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids.

“…The striking serum dependence of colony growth for synoviocytes from both rat and human arthritic joints and the known presence of certain cytokines in serum and rheumatoid synovial fluid led us to examine the effects of various cytokines on the anchorage-independent growth. Previous work has demonstrated PDGF, EGF, and insulinlike growth factors in serum (16,17), and rheumatoid synovial fluids are known to contain IL-i (18,19), TNF-alpha (20), IFN-gamma (21, 22), EGF (23), PDGF, and TGF-beta (24). Therefore, the effects of these cytokines on anchorage-independent synoviocyte growth were analyzed.…”

Type vi collagen—specific messenger rna is expressed constitutively by cultured human synovial fibroblasts and is suppressed by interleukin–1

“…In view of the previously demonstrated matrix-synthesizing capabilities of the human synovial fibroblast, we hypothesized that this cell may be a rich source of type VI collagen in synovium. Interleukin-I (IL-l), a cytokine whose presence in synovial fluid and synovial tissues in a variety of arthropathies is well documented (13), is known to influence a number of articular cell functions. IL-1, for example, is not only a potent stimulus for the synthesis and release of prostaglandins and proteases from synovial fibroblasts and chondrocytes (3,4), but it also appears to play a role in regulating the synthesis of fibrillar collagens by these cells (14,15).…”

Transforming growth factor beta 1 regulates production of acute-phase proteins.

“…Among these alterations are changes in hepatic synthesis of a number of plasma proteins, referred to as acute-phase proteins; synthesis of some proteins, the positive acute-phase proteins, increases, while synthesis of others, the negative acute-phase proteins, decreases. Studies in primary hepatocyte cultures and hepatoma cell lines have shown that hepatic synthesis of human acute-phase proteins can be influenced by several cytokines including interleukin 6 (IL-6), a major inducer ofacute-phase changes, interleukins la and -p8 (IL-1), cachectin/tumor necrosis factor a (TNF), interferon y, and leukemia inhibitory factor (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). One cytokine can modulate the effect of other cytokines in human model systems-e.g., IL-1 diminishes the inducing effect of IL-6 on fibrinogen synthesis (7,12,18) and interferon y…”