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- Title
Neutralizing IL-21 and IL-15 Inhibits Pro-inflammatory Cytokine Production in Rheumatoid Arthritis.
- Authors
Andersson, A. K.; Feldmann, M.; Brennan, F. M.
- Abstract
Interleukin (IL)-21 and IL-15 belong to the common γ-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)α, IL-6 and IL-1β 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 μg/ml) significantly reduced TNFα production by 50%, IL-6 by 57% and IL-1β by 81%. Anti-IL-15 antibody (5 μg/ml) significantly inhibited TNFα release by 51%, IL-6 by 37% and IL-1β 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.
- Subjects
CYTOKINES; CELLULAR immunity; IMMUNOREGULATION; IDIOTYPIC networks; IMMUNOMODULATORS; MESSENGER RNA
- Publication
Scandinavian Journal of Immunology, 2008, Vol 68, Issue 1, p103
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.1365-3083.2008.02118.x