Objectives: To identify the mechanism of IL-7- stimulated TNFα production and to determine the relationship between intra-articular IL-7 and TNF& [alpha] expression levels in rheumatoid arthritis (RA) patients. In addition the effect of TNFα blockade on IL-7 activity and on IL-7 levels was studied.
Methods: The effect of IL-7 on isolated CD4+ T cells and CD14+ monocytes/macrophages was studied. IL-7 and TNFα levels were measured in the synovial fluid of patients with RA. In RA synovial tissue IL-7 and TNFα expression was assessed in addition to IL-1β, numbers of inflammatory cells and adhesion molecule expression. The extent to which TNFα blockade could prevent IL-7-induced lymphocyte responses was studied in vitro. In addition, regulation of serum IL-7 levels was studied upon anti-TNFα therapy (Adalimumab).
Results: IL-7 induced cell contact-dependent TNF& [alpha] production by cocultures of T cells and monocytes, but not by T cells and monocytes cultured separately. IL-7 and TNFα levels in RA synovial fluid and synovial tissue significantly correlated. IL-7- stimulated lymphocyte responses were not inhibited by TNFα blockade. Circulating IL-7 levels were significantly reduced in patients that successfully responded to anti-TNFα therapy. However, IL-7 levels persisted in non-responders.
Conclusion: The present data indicate that IL-7 could be an important inducer of T-cell-dependent TNF& [alpha] production in RA joints. This may contribute to the correlation of intra-articular IL-7 and TNFα in these joints. Furthermore, the persistence of IL-7- induced inflammatory activity upon TNFα blockade in vitro and persistence of IL-7 levels and disease activity in anti-TNFα non-responders suggest that IL-7 might additionally promote TNFα-independent inflammation.
- T cells
- TNF alpha
- rheumatoid arthritis