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

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Ann Rheum Dis. 2006 Dec 21; [Epub ahead of print]

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

patients with rheumatoid arthritis.

van Roon JA, Hartgring SA, Wenting-van Wijk M, s KM, Tak PP, Bijlsma

JW, Lafeber FP.

University Medical Center Utrecht, Netherlands.

OBJECTIVES: To identify the mechanism of IL-7- stimulated TNFalpha

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 TNFalpha 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 TNFalpha levels were measured in

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

TNFalpha expression was assessed in addition to IL-1beta, numbers of

inflammatory cells and adhesion molecule expression. The extent to which

TNFalpha blockade could prevent IL-7-induced lymphocyte responses was

studied in vitro. In addition, regulation of serum IL-7 levels was studied

upon anti-TNFalpha 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

TNFalpha levels in RA synovial fluid and synovial tissue significantly

correlated. IL-7- stimulated lymphocyte responses were not inhibited by

TNFalpha blockade. Circulating IL-7 levels were significantly reduced in

patients that successfully responded to anti-TNFalpha 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 TNFalpha in these

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

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

activity in anti-TNFalpha non-responders suggest that IL-7 might

additionally promote TNFalpha-independent inflammation.

PMID: 17185327

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

7185327

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