Article Text

Download PDFPDF
Persistence of interleukin 7 activity and levels on tumour necrosis factor α blockade in patients with rheumatoid arthritis
  1. Joel A G van Roon1,
  2. Sarita A Y Hartgring1,
  3. Marion Wenting-van Wijk1,
  4. Kim M G Jacobs1,
  5. Paul-Peter Tak2,
  6. Johannes W J Bijlsma1,
  7. Floris P J G Lafeber1
  1. 1Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to:
    Dr J A G van Roon
    Department of Rheumatology and Clinical Immunology (F02.127), University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; J.vanRoon{at}


Objectives: To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor α (TNFα) production and to determine the relationship between intra-articular IL7 and TNFα expression levels in patients with rheumatoid arthritis (RA). In addition, the effect of TNFα blockade on IL7 activity and on IL7 levels was studied.

Methods: The effect of IL7 on isolated CD4 T cells and CD14 monocytes/macrophages was studied. IL7 and TNFα levels were measured in the synovial fluid of patients with RA. In RA synovial tissue, IL7 and TNFα expression was assessed in addition to IL1β, numbers of inflammatory cells and adhesion molecule expression. The extent to which TNFα blockade could prevent IL7-induced lymphocyte responses was studied in vitro. In addition, regulation of serum IL7 levels on anti-TNFα therapy (adalimumab) was studied.

Results: IL7 induced cell contact-dependent TNFα production by cocultures of T cells and monocytes, but not by T cells and monocytes cultured separately. IL7 and TNFα levels in RA synovial fluid and synovial tissue significantly correlated. IL7-stimulated lymphocyte responses were not inhibited by TNFα blockade. Circulating IL7 levels were significantly reduced in patients who successfully responded to anti-TNFα treatment. However, IL7 levels persisted in non-responders.

Conclusion: The present data suggest that IL7 is an important inducer of T cell-dependent TNFα production in RA joints. This may contribute to the correlation of intra-articular IL7 and TNFα in these joints. Furthermore, the persistence of IL7-induced inflammatory activity on TNFα blockade in vitro and persistence of IL7 levels and disease activity in anti-TNFα non-responders suggest that IL7 might additionally promote TNFα-independent inflammation.

  • FACS, fluorescence-activated cell sorting
  • IL, interleukin
  • JIA, juvenile idiopathic arthritis
  • mAbs, monoclonal antibodies
  • MC, mononuclear cells
  • PB, peripheral blood
  • RA, rheumatoid arthritis
  • SF, synovial fluid
  • SFMC, synovial fluid mononuclear cells
  • TNFα, tumour necrosis factor α

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.