Neutralizing IL-21 and IL-15 inhibits pro-inflammatory cytokine production in rheumatoid arthritis

Scand J Immunol. 2008 Jul;68(1):103-11. doi: 10.1111/j.1365-3083.2008.02118.x. Epub 2008 May 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation / immunology*
  • Inflammation Mediators / immunology
  • Interleukin-15 / antagonists & inhibitors
  • Interleukin-15 / immunology*
  • Interleukins / antagonists & inhibitors
  • Interleukins / immunology*
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology


  • Cytokines
  • Inflammation Mediators
  • Interleukin-15
  • Interleukins
  • interleukin-21