RESEARCH - Persistence of IL-7 activity and IL-7 levels upon TNF-alpha blockade in patients with RA

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Ann Rheum Dis. Published Online First: 21 December 2006.

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Extended Report

Persistence of IL-7 activity and IL-7 levels upon TNF & [alpha] blockade in

patients with rheumatoid arthritis

A.G. van Roon 1*, Sarita A.Y. Hartgring 1, n Wenting-van Wijk 1,

Kim M.G. s 1, - Tak 2, Johannes WJ Bijlsma 1 and Floris P.J.G.

Lafeber 1

1 University Medical Center Utrecht, Netherlands

2 AMC Amsterdam, Netherlands

Abstract

Objectives: To identify the mechanism of IL-7- stimulated TNF 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 TNF 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 TNF levels were measured in the

synovial fluid of patients with RA. In RA synovial tissue IL-7 and TNF

expression was assessed in addition to IL-1, numbers of inflammatory cells

and adhesion molecule expression. The extent to which TNF blockade could

prevent IL-7-induced lymphocyte responses was studied in vitro. In addition,

regulation of serum IL-7 levels was studied upon anti-TNF 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 TNF levels in RA synovial fluid and synovial

tissue significantly correlated. IL-7- stimulated lymphocyte responses were

not inhibited by TNF blockade. Circulating IL-7 levels were significantly

reduced in patients that successfully responded to anti-TNF 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 TNF in these

joints. Furthermore, the persistence of IL-7- induced inflammatory activity

upon TNF blockade in vitro and persistence of IL-7 levels and disease

activity in anti-TNF non-responders suggest that IL-7 might additionally

promote TNF-independent inflammation.

http://ard.bmj.com/cgi/content/abstract/ard.2006.062547v1?papetoc

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