Skip Navigation


Rheumatology Advance Access originally published online on September 7, 2004
Rheumatology 2005 44(1):24-31; doi:10.1093/rheumatology/keh398
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
44/1/24    most recent
keh398v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (13)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Dalbeth, N.
Right arrow Articles by Hall, F. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dalbeth, N.
Right arrow Articles by Hall, F. C.
Related Collections
Right arrow Experimental Arthritis
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Rheumatology Vol. 44 No. 1 © British Society for Rheumatology 2004; all rights reserved

PAPER

The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis

N. Dalbeth1,2, J. Edwards3, S. Fairchild4, M. Callan1,2 and F. C. Hall2,4

1 Division of Medicine, Imperial College London, London, 2 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, 3 Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford and 4 University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.

Correspondence to: N. Dalbeth, Department of Immunology, Imperial College London, Commonwealth Building, Hammersmith Campus, Du Cane Rd, London W12 0NN, UK. E-mail: n.dalbeth{at}ic.ac.uk

Objectives. In addition to its vasoactive effects, angiotensin II has proinflammatory properties. Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin II and could therefore act as anti-inflammatory agents. Here we investigated the capacity of the ACE inhibitor quinapril to modulate inflammatory arthritis.

Methods. We studied the effect of quinapril on disease activity in mice with collagen-induced arthritis (CIA). Mice received oral quinapril (10 mg/kg/day) at the time of arthritis induction (prophylaxis protocol) or at the onset of mild arthritis (therapy protocol). Concentrations of immunoglobulin G (IgG) subtypes specific for bovine Type II collagen and TNF-{alpha} were measured by enzyme-linked immunoassay.

Results. Quinapril significantly diminished the activity of CIA when given as prophylaxis or therapy (prophylaxis protocol, P<0.001; therapy protocol P = 0.002). Antigen-specific IgG2a antibodies were reduced by 52% (P = 0.02) in the quinapril prophylaxis protocol. Suppression of arthritis by quinapril was associated with reduced articular expression of TNF-{alpha} by 68% (P = 0.01) in the prophylaxis protocol and 27% (P = 0.06) in the therapy protocol. Quinapril therapy also inhibited expression of splenocyte TNF-{alpha} production following lipopolysaccharide (LPS) in vitro stimulation by 59% (P = 0.02). In parallel human in vitro experiments, ACE inhibition suppressed LPS-stimulated production of TNF-{alpha} by monocytes. In order to confirm that the action of quinapril occurred predominantly through suppression of angiotensin II, parallel experiments with the angiotensin receptor antagonist candesartan cilexetil demonstrated that this agent also inhibited disease activity in CIA.

Conclusions. These data suggest that angiotensin II is a mediator of chronic inflammation and that ACE inhibition may have therapeutic effects in human inflammatory arthritis.

KEY WORDS: Angiotensin II, Inflammation, Monocytes/Macrophages, Rheumatoid Arthritis


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera
Peptide Hormone Regulation of Angiogenesis
Physiol Rev, October 1, 2009; 89(4): 1177 - 1215.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Platten, S. Youssef, E. M. Hur, P. P. Ho, M. H. Han, T. V. Lanz, L. K. Phillips, M. J. Goldstein, R. Bhat, C. S. Raine, et al.
Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity
PNAS, September 1, 2009; 106(35): 14948 - 14953.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y. Okunuki, Y. Usui, N. Nagai, T. Kezuka, S. Ishida, M. Takeuchi, and H. Goto
Suppression of Experimental Autoimmune Uveitis by Angiotensin II Type 1 Receptor Blocker Telmisartan
Invest. Ophthalmol. Vis. Sci., May 1, 2009; 50(5): 2255 - 2261.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
M E Perry, M M Chee, W R Ferrell, J C Lockhart, and R D Sturrock
Angiotensin receptor blockers reduce erythrocyte sedimentation rate levels in patients with rheumatoid arthritis
Ann Rheum Dis, November 1, 2008; 67(11): 1646 - 1647.
[Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
L. Pattacini, B. Casali, L. Boiardi, N. Pipitone, L. Albertazzi, and C. Salvarani
Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-{kappa}B pathway
Rheumatology, August 1, 2007; 46(8): 1252 - 1257.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
F. C. Hall and N. Dalbeth
Disease modification and cardiovascular risk reduction: two sides of the same coin?
Rheumatology, December 1, 2005; 44(12): 1473 - 1482.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.