Synovium, rheumatoid synovial cells

Rheumatoid arthritis is a systemic autoimmune disorder produced by an inflammatory response of the synovium of the joints and is accompanied by hyperplasia of synovial cells, excess of synovial fluid, and apparition of fibrous tissue in the synovium, leading together to the destruction of the articular cartilage and ankylosis or fusion of the joints. In a pilot study published... 

Articulated joints between bones, for example at the knee, are covered in a capsule enclosing a space, which contains synovial fluid. The lining of the capsule is composed by the synovial membrane it is this synovium that becomes inflamed in rheumatoid arthritis (RA). Secretions produced by inflammatory cells (lymphocytes, macrophages... 

In rheumatoid arthritis, immune complexes are deposited in the affected joints, causing an inflammatory response that is amplified by eicosanoids. Lymphocytes and macrophages accumulate in the synovium, whereas leukocytes localize mainly in the synovial fluid. The major eicosanoids produced by leukocytes are leukotrienes, which facilitate T-cell proliferation and act as chemoattractants. Human macrophages synthesize the COX products PGE2 and TXA2 and large amounts of leukotrienes. 

IL-18 augments T- and NK-cell maturation, cytotoxicity and cytokine production. It stimulates TH differentiation, promotes secretion of TNF-a, IFN-y and GM-CSF and enhances NK cell cytotoxicity by increasing FasL expression. IL-8-mediated neutrophil chemotaxis is promoted by IL-18 via its effects on TNF-a and IFN-y, which are stimulatory in action. It plays an important role in maintaining synovial inflammation and inducing joint destruction in rheumatoid arthritis. In synovium of patients with rheumatoid arthritis, enhanced levels of TNF-a and IL-1 are associated with augmented expression of IL-18. 

T. wilfordii has been used as a traditional medicine in China for many centuries. The plant has also been used to treat rheumatoid arthritis and spondylitis [92]. It has been reported that there is a strong relationship between the production of interleukin - 1 (IL-1) by the synovium and the degree of inflammation of the arthricular synovial membrane in rheumatoid artritis [93-95]. Regeol A (76), B (3) and C (77) [27], isolated from T. wilfordii var. regelii showed moderate to low inhibitory activity for IL-1 a and IL-lp release from lipopolysaccharide-stimulated human peripheral mononuclear cells compared to prednisolone as a reference compound. 

Buckley, C.D., Amft, N., Bradfleld, P.F., Pilling, D., Ross, E., Arenzana-Seisdedos, F., Amara, A., Curnow, S.J., Lord, J.M., Scheel-Toellner, D., and Salmon, M. (2000) Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. Journal of Immunology (Baltimore, Md 1950), 165, 3423-3429. 

Fia. 19. Synovial collagenolytifi activity as a function of DNA content of the synovium after 4 days of culture. Note that cells of synovia tissues from rheumatoid arthritis patients produce substantially more collagcnaso than do cells of synovial tissues from non rheumatoid patients. A, Nonrheumatoid arthritis patients., Rheumatoid arthritis patients. (Lazarus ei al, 1968a.)... 

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