Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


(2252)adrenomedullin Shifts Cytokine Balance from Th1 to Th2, Reduces IL-17A Expressions and Modulates Treg Cells in Collagen-Induced Arthritis.

Kioon5,  Marie-Dominique Ah, Asensio5,  Carine, Ea5,  Korng, Rulle1,  Sandrine, Falgarone1,  Géraldine, Collet4,  Corinne, Launay3,  Jean-Marie

EA 4222, Paris 13 University, Bobigny, France, Metropolitan
Hopital Lariboisiere, Paris, France
Paris 5 University, Paris, France, Metropolitan
Paris 5 University, Bobigny, France, Metropolitan
UMR-S606 Inserm, Paris Diderot University, Paris, France, Metropolitan

Purpose:

Rheumatoid arthritis is an inflammatory disease characterized by an increase in pro-inflammatory cytokine production due to activated Th1 and Th17 cells, and Treg dysregulation. Depending on cell types, adrenomedullin (AM) acts as a pro- or anti-inflammatory peptide in vitro. It exerts anti-inflammatory effects in vivo: AM reduces IL-1, IL-6 and TNF-a in septic mice and reduces collagen-induced arthritis (CIA) by up-regulating Treg cells. (22–52)AM, a fragment peptide which binds to AM receptors, acts also as an antagonist or agonist of ADM in vitro but its in vivo effects are unknown. Our aim was to evaluate effects of (22–52)AM on arthritis score, seric and articular cytokines expression in CIA.

Methods:

CIA DBA/1 mice were treated with 1.2 mg/g (22–52)AM or saline (control) as soon as arthritis occurred. Animals were sacrificed at day 45 (D45), joints were processed for histology and protein studies and spleens for Treg expression. Expression of cytokines (ELISA) was studied in joint tissues and in sera.

Results:

At D24 post-immunization, control CIA saline-treated mice started to develop arthritis as shown by arthritic score (ranging from 2 to 11 from D24–45). At sacrifice, (22–52)AM had decreased arthritic score compared to saline (5.8±2 vs 11±3, respectively; p<0.05). Incidence of arthritis was reduced by 25 % with (22–52)AM. Histological scores were decreased with (22–52)ADM compared to control (0.56±0.04 vs 3.78±0.26, p<0.05). Compared to naïve mice, saline-treated CIA mice had significantly higher serum levels of the proinflammatory cytokines TNF-a, IL-6, IL-17A). (22–52)AM completely abrogated this increase The broad systemic antiinflammatory activity of AM and (22–52)AM was accompanied by down-regulation of Th1 (TNF-a, IL-6) and Th17 (IL-17A) cytokine expression in knee extracts and up-regulation of anti-inflammatory cytokines (IL-10, IL-4). Furthermore, the number of Treg cells expressing CD4+CD25+Foxp3 was decreased in control CIA mice vs naïve mice. (22–52)AM had no effect on number of Treg cells as compared to CIA control mice but, (22–52)AM treatment significantly increased serum IL-2 level in CIA mice.

Conclusions:

(22–52)AM, along with reduced clinical and histological arthritis score in CIA, dramatically decreased serum and articular pro-inflammatory cytokines and triggered a robust increase in anti-inflammatory cytokines in CIA mice. (22–52)AM did not modulate the number of CD4+CD25+Foxp3 Treg cells but, increased Treg functions, as evidenced by increased IL-2 production, a marker of Treg activity.

To cite this abstract, please use the following information:
Kioon, Marie-Dominique Ah, Asensio, Carine, Ea, Korng, Rulle, Sandrine, Falgarone, Géraldine, Collet, Corinne, et al; (2252)adrenomedullin Shifts Cytokine Balance from Th1 to Th2, Reduces IL-17A Expressions and Modulates Treg Cells in Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1707
DOI: 10.1002/art.29472

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