Interferon β stimulates interleukin 1 receptor antagonist production in human articular chondrocytes and synovial fibroblasts

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Abstract
Background: Interferon (IFN) β displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however. Objective: To investigate the effects of IFNβ on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts. Methods: Chondrocytes and synovial fibroblasts were stimulated with IFNβ alone or in combination with interleukin (IL) 1β. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction. Results: In chondrocytes, IFNβ alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1β. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1β and IFNβ. Consistently, IL1β and IFNβ induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNβ alone dose dependently increased IL1Ra secretion. In addition, IFNβ enhanced the stimulatory effect of IL1β on IL1Ra production. In synovial cell lysates, IFNβ and IL1β also increased IL1Ra levels. Consistently, IFNβ and IL1β induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts. Conclusion: IFNβ increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.