Objective. To quantify interleukin-1 receptor antagonist (IL-lra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells.Methods. IL-la, IL-lP, and IL-lra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-lra (sILIra) and the alternatively spliced intracellular form (icIL-lra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques.Results. IL-la, IL-lP, and IL-lra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the l&lOO-fold excess of IL-lra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-lra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-lra but secreted little IL-lra into the culture supernatants. RT-PCR showed that icIL-lra
Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.
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