- Paper Report
- Open Access
IL-1a and arthritis
- Diane Marshall1
© Biomed Central Ltd 2001
- Received: 9 July 2001
- Published: 31 July 2001
Interleukin (IL)-1 has been implicated in the pathogenesis of rheumatoid arthritis (RA) and is thought particularly to play a central role in joint destruction. Elevated levels of IL-1 are present in the synovial fluid, synovial membrane and cartilage-pannus junction of arthritic joints. The relative contributions of IL-1 and tumour necrosis factor (TNF)-a and the roles of T-cell-independent and antigen-specific T-cell-dependent mechanisms in rheumatoid synovitis are still unclear. The authors investigated the potential direct effect of IL-1a on arthritis in mice transgenic (Tg) for human IL-1a (hIL-1a).
Overexpression of hIL-1a was detected at both the mRNA and protein levels in a wide variety of tissues, including synoviocytes and bone marrow (BM) macrophages. The hIL-1a secreted by synoviocytes and BM macrophages was shown to be biologically active. Synovial hyperplasia (resulting from accumulation of cells with a macrophage-like morphology), loss of cartilage, bone erosion, fibrin deposits and the formation of pannus-like tissue were revealed in 8-week-old mice. Nearly 80% of freshly isolated synoviocytes were positive for the F4/80 antigen. The majority of the cells infiltrating below and within the synovium were polymorphonuclear neutrophils (PMNs) and expressed high levels of Gr-1, indicating they were mature, tissue-degrading PMNs. Granulocyte-macrophage colony-stimulating factor was found to be twofold to threefold higher in supernatants from synoviocytes and BM macrophages and in the sera of Tg mice compared to sera of non-Tg littermates.
Generation of transgenic mice, cell culture, northern blot analysis, immunoprecipitation, SDS-PAGE, ELISA, bioassay, immunohistochemistry, flow cytometry, histological analysis
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