Interferon‐γ induces expression of interleukin‐18 binding protein in fibroblast‐like synoviocytes

Objective. To investigate expression of the endogenous antagonist of interleukin 18 (IL‐18) bioactivity, IL‐18 binding protein isoform a (IL‐18BPa), in fibroblast‐like synoviocytes (FLS). Methods. Long‐term cultured FLS from rheumatoid arthritis (RA), osteoarthritis (OA) and spondylarthropathy patients were analysed for spontaneous and cytokine‐induced IL‐18BPa expression. Messenger RNA and release of IL‐18BPa were assessed by semi‐quantitative and quantitative real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) as well as immunoblot analysis, respectively. Results. All investigated FLS cultures expressed low amounts of IL‐18BPa transcripts. However, there was no detectable release of IL‐18BPa from unstimulated synoviocytes. Of the investigated cytokines, only interferon (IFN)‐γ markedly up‐regulated IL‐18BPa mRNA levels. Induction was accompanied by release of IL‐18BPa immunoreactvity from FLS. Conditioned media from IFN‐γ‐stimulated FLS cultures reduced IL‐12/IL‐18‐dependent IFN‐ production by peripheral blood mononuclear cells. Conclusion. The present data imply that IFN‐‐activated synoviocytes mediate a negative feedback loop via IL‐18BPa, which may limit IL‐18 biological activity in arthritis.