RESEARCH - TNF blockade increases lymphangiogenesis in murine and human arthritic joints

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Ann Rheum Dis. Published Online First: 3 January 2008.

doi:10.1136/ard.2007.083394

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Extended Report

TNF blockade increases lymphangiogenesis in murine and human arthritic

joints

Karin Polzer 1, Dominique Baeten 2, Afschin Soleiman 3, Jörg Distler 1,

le M Gerlag 2, P Tak 2, Georg Schett 1 and Jochen Zwerina 1*

1 Department of Internal Medicine 3 and Institute for Clinical Immunology,

University of Erlangen, Germany

2 Division of Clinical Immunology and Rheumatology, Academic Medical

Center/University of Amsterdam, Netherlands

3 Medial University of Vienna, Austria

Abstract

Objective: To investigate the presence and regulation of lymphatic vessels

in inflamed joints of mice with experimental arthritis as well as patients

with rheumatoid arthritis (RA) and spondyloarthritis (SpA).

Methods: Lymphatic vessels and blood vessels were assessed in synovial

tissue of human tumor necrosis factor transgenic (TNFtg) mice and synovial

biopsies from patients with RA and SpA by immunohistochemistry for

podoplanin and CD31, respectively. Assessments were performed before and

after TNF blockade in all biopsies.

Results: Lymphatic vessels were abundantly present in the synovial tissue of

hTNFtg mice as well as RA and SpA patients. The number of lymphatic vessels

was positively related to the severity of synovial inflammation. Treatment

with infliximab led to an increase in formation of lymphatic vessels in

murine and human inflammatory tissue.

Conclusion: This study shows that TNF blockade promotes the proliferation of

lymphatic vessels in the inflamed synovium of RA and SpA. This finding leads

to the assumption that promotion of lymphangiogenesis may play an important

role in efflux of cells and fluid out of the inflamed tissue.

http://ard.bmj.com/cgi/content/abstract/ard.2007.083394v1?papetoc

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