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
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