2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005121359v1 17/5/1243    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feldmann, M. Articles by Pusey, C. D. Search for Related Content PubMed PubMed Citation Articles by Feldmann, M. Articles by Pusey, C. D.

Is There a Role for TNF- in Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases

Marc Feldmann^* and Charles D. Pusey

^* Kennedy Institute of Rheumatology Division, Charing Cross Campus; and Renal Section, Division of Medicine, Hammersmith Campus, Imperial College London, United Kingdom

Address correspondence to: Prof. Charles D. Pusey, Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK. Phone: +44-20-8383-3152; Fax: +44-20-8383-2062; E-mail: c.pusey{at}imperial.ac.uk

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis and immune-mediated pulmonary renal syndrome. Now that the acute manifestations of the disease generally can be controlled with immunosuppressive drugs, ANCA-associated vasculitis has become a chronic and relapsing inflammatory disorder. The need to develop safer and more effective treatment has led to great interest in the mediators of chronic inflammation. There are many lessons to be learned from studies of other chronic inflammatory diseases, particularly rheumatoid arthritis (RA). The identification of a TNF-–dependent cytokine cascade in the in vitro cultures of synovium in joints of patients with RA led to studies of TNF blockade in experimental models of arthritis and subsequently to clinical trials. These have culminated in the widespread introduction of anti-TNF therapy not only in RA but also in Crohn disease, ankylosing spondylitis, and several other chronic inflammatory disorders. Following a similar investigative pathway, studies that show the importance of TNF production by leukocytes and intrinsic renal cells in glomerulonephritis have been followed by the demonstration of the effectiveness of TNF blockade in several experimental models of glomerulonephritis and vasculitis. In experimental autoimmune vasculitis, improvement in disease was paralleled by a reduction in leukocyte transmigration, as demonstrated by intravital microscopy. The benefit of infliximab (a mAb to TNF) in ANCA-associated vasculitis was recently reported in a prospective open-label study. However, the use of etanercept (a soluble TNF receptor fusion protein) was not found to be of significant benefit in a randomized, controlled trial in patients with Wegener granulomatosis. Therefore, there is a need for further evaluation of the use of anti-TNF antibodies in patients with ANCA-associated glomerulonephritis.

This article has been cited by other articles:

				M. Lauterbach, P. O'Donnell, K. Asano, and T. N. Mayadas Role of TNF priming and adhesion molecules in neutrophil recruitment to intravascular immune complexes J. Leukoc. Biol., June 1, 2008; 83(6): 1423 - 1430. [Abstract] [Full Text] [PDF]

				I Sabroe, L C Parker, P M A Calverley, S K Dower, and M K B Whyte Pathological networking: a new approach to understanding COPD Postgrad. Med. J., May 1, 2008; 84(991): 259 - 264. [Abstract] [Full Text] [PDF]

				K Polzer, A Soleiman, W Baum, R Axmann, J Distler, K Redlich, A Kilian, G Kronke, G Schett, and J Zwerina Selective p38MAPK isoform expression and activation in antineutrophil cytoplasmatic antibody-associated crescentic glomerulonephritis: role of p38MAPK{alpha} Ann Rheum Dis, May 1, 2008; 67(5): 602 - 608. [Abstract] [Full Text] [PDF]

				I. Sabroe, L. C. Parker, S. K. Dower, and M. K. B. Whyte Practical and Conceptual Models of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, December 1, 2007; 4(8): 606 - 610. [Abstract] [Full Text] [PDF]

				I. Sabroe, L. C Parker, P. M A Calverley, S. K Dower, and M. K B Whyte Pathological networking: a new approach to understanding COPD Thorax, August 1, 2007; 62(8): 733 - 738. [Abstract] [Full Text] [PDF]

				D. Xing, W. Feng, A. P. Miller, N. M. Weathington, Y.-F. Chen, L. Novak, J. E. Blalock, and S. Oparil Estrogen modulates TNF-{alpha}-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-beta activation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2607 - H2612. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673