Angiotensin receptor blockers suppress antigen-specific T cell responses and ameliorate collagen-induced arthritis in mice.
OBJECTIVE
The renin-angiotensin system plays an important role in the regulation of cardiovascular, renal, and endocrine functions. Recent studies have demonstrated that angiotensin II has proinflammatory effects that may contribute to the pathogenesis of immune-mediated diseases. We used the collagen-induced arthritis (CIA) model to investigate the influence of angiotensin II receptor blockers (ARBs) on antigen-specific immune responses and determine whether ARBs have preventive or therapeutic effects on the development of arthritis.


METHODS
We administered ARBs (olmesartan, candesartan, and telmisartan) to mice and evaluated antigen-specific T cell proliferation and cytokine production following immunization with ovalbumin (OVA) or type II collagen in Freund's complete adjuvant (CFA) or aluminum hydroxide (alum). Next, we induced CIA in DBA/1 mice and administered olmesartan. The severity and incidence of arthritis were scored according to clinical manifestations, and joint tissue sections were examined histopathologically.


RESULTS
ARBs severely suppressed lymphocyte proliferation and interferon-gamma production in mice immunized with OVA or type II collagen in CFA. Olmesartan also suppressed lymphocyte proliferation in mice immunized with ovalbumin in alum. In the CIA model, olmesartan reduced the mean arthritis score and the incidence of severe arthritis, even when it was administered only after disease onset. Histopathologic findings for joint destruction were improved in olmesartan-treated mice.


CONCLUSIONS
ARBs suppressed antigen-specific immune responses for Th1 and Th2 in vivo. Furthermore, olmesartan suppressed the development of severe arthritis and joint destruction in the CIA model. These findings suggest that ARBs may have therapeutic potential in rheumatoid arthritis.
Sagawa
Kayo
K
University of Tokyo, Tokyo, Japan.
Nagatani
Katsuya
K
Komagata
Yoshinori
Y
Yamamoto
Kazuhiko
K
D047228:Angiotensin II Type 1 Receptor Blockers / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000276:immunology; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D001562:Benzimidazoles / Q000276:immunology / Q000627:therapeutic use; D001565:Benzoates / Q000276:immunology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D003094:Collagen / Q000009:adverse effects; D005260:Female; D007093:Imidazoles / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D023421:Models, Animal; D000068557:Olmesartan Medoxomil; D013601:T-Lymphocytes / Q000276:immunology; D000077333:Telmisartan; D013777:Tetrazoles / Q000276:immunology / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology
D047228:Angiotensin II Type 1 Receptor Blockers; D000941:Antigens; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D003094:Collagen; C081643:candesartan; D000077333:Telmisartan