|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1995 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1994 : ¥1,400,000 (Direct Cost : ¥1,400,000)
The expression of interleukin-10 and its pathogenic role in rheumatoid arthritis (RA) was investigated. Concentrations of IL-10 in both serum and synovial fluid from RA patients were greater compared to those of osteoarthritis patients. Synovial tissues in RA more strongly expressed IL-10 mRNA than in OA, and spontaneously produced higher levels of IL-10. By Immunohistochemical staining and detection of IL-10 in isolated macrophages, fibroblasts, and T cells from RA synovium, macrophages in both the lining and sublining layer are major sources of this cytokine. IL-10 markedly inhibited the production of inflammatory cytokines such as IL-1 and TNF-α by RA synovium, but both cytokines were potent inducer of IL-10. On the other hand, T cell-derived anti-inflammatory cytokines, IL-4 and Il-13, are less efficient in inhibiting synovial inflammatory cytokines, 7but are able to inhibit proliferation of RA synovial fibroblasts. However, their expression in RA joint is extremely limited IL-10 expression was associated with levels of IgG-rheumatoid factor in RA. These results indicate that IL-10 may be mostly responsible for downregulation of chronic inflammation and rheumatoid factor production in RA, although its synoival expression if not sufficient to control the disease activity.
Of IL-6-type cytokines, large amounts of IL-6, IL-11, and LIF were produced mainly by IL-1 or TNF-activated fibroblasts, whereas oncostatin M was exclusively by macrophages in RA joints. However, only IL-6 was circulating at significant levels in association with raised levels of serum CRP levels, indicating its contribution to systemic inflammatory reactions such as acute-pahse reactant production by liver.