Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regulation by interferon gamma

Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1-induced bone and cartilage degradation and in patients with diseases involving IL-1.