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Interleukin IL-21 and IL-15 belong to the common gamma-chain receptor family. IL-15 represents a novel therapeutic target in rheumatoid arthritis (RA), whereas less is known about the role of IL-21 in human inflammatory diseases. We have analysed the effects of blocking IL-21 and IL-15 on spontaneous production of pro-inflammatory cytokines in RA synovial cell cultures. RA synovial membrane cells were cultured in the presence of an IL-21R-Fc chimera or a neutralizing IL-15 antibody and production of tumour necrosis factor (TNF)alpha, IL-6 and IL-1beta was measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-21 and IL-15 in RA synovium was measured by RT-PCR and ELISA. mRNA for IL-21 and IL-21R was detected in the culture cell lysates. Protein for IL-15 was found at detectable levels in the cell lysates. Both the IL-21R-Fc chimera and anti-IL-15 antibody inhibited cytokine release, although substantially more IL-21R-Fc was needed. IL-21R-Fc at the highest dose (100 microg/ml) significantly reduced TNFalpha production by 50%, IL-6 by 57% and IL-1beta by 81%. Anti-IL-15 antibody (5 microg/ml) significantly inhibited TNFalpha release by 51%, IL-6 by 37% and IL-1beta by 82% in line with previous published observations. The data confirm that IL-15 plays a role in RA and suggests that IL-21 is also involved in driving the pro-inflammatory cytokine response in RA.

Original publication

DOI

10.1111/j.1365-3083.2008.02118.x

Type

Journal article

Journal

Scandinavian journal of immunology

Publication Date

07/2008

Volume

68

Pages

103 - 111

Addresses

Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, London, UK.

Keywords

Synovial Membrane, Cells, Cultured, Humans, Arthritis, Rheumatoid, Inflammation, Inflammation Mediators, Interleukins, Interleukin-15, Cytokines, Enzyme-Linked Immunosorbent Assay, Reverse Transcriptase Polymerase Chain Reaction, Adult, Aged, Middle Aged, Female, Male