Anti-Interleukin-1 Agents in Adult Onset Still's Disease

Author:

Giampietro Cecilia1,Fautrel Bruno23

Affiliation:

1. Department of Internal Medicine, University of L’Aquila, L’Aquila, Italy

2. School of Medicine, University Paris 6-Pierre et Marie Curie, 75013 Paris, France

3. Department of Rheumatology, AP-HP, Pitié-Salpêtrière University Hospital, 75013 Paris, France

Abstract

Interleukin 1β(IL-1β) is emerging as a master mediator of adult onset Still’s disease (AOSD) pathogenesis. This pleiotropic cytokine, whose expression is under the control of the inflammasome pathway, has a wide type of effects. As a key mediator of innate immunity is a potent pyrogen and facilitates neutrophilic proliferation and diapedesis into the inflamed tissues, which are key AOSD manifestations. The study of proinflammatory cytokines profiles in sera and pathological tissues of AOSD patients has shown elevated levels of IL-1β, these levels being highly correlated with disease activity and severity. These experimental evidences and the analogy with other autoinflammatory diseases that share with AOSD clinical and biological characteristics have suggested the blockade of IL-1βas a possible new therapeutic option for the AOSD, especially in conventional therapy resistant cases. Anakinra, the first anti-IL-1 agent put on the market, has demonstrated capable to induce a rapid response sustained over time, especially in systemic forms, where anti-TNFαfailed to control symptoms. While a growing number of evidences supports the utilisation of anakinra in AOSD, a new generation of anti-IL1βantagonists is developing. Canakinumab and rilonacept, thanks to their higher affinity and longer half-life, could improve the management of this invalidating disease.

Publisher

Hindawi Limited

Subject

Immunology and Allergy

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