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AB0055 Il-1 beta and CASPASE-1 p45 expression in peripheral blood mononuclear cells of patients with adult-onset still's disease
  1. S Bindoli,
  2. F Fabris,
  3. L Punzi,
  4. P Galozzi,
  5. P Sfriso
  1. Rheumatology Unit- Department of Medicine, University of Padova, Padova, Italy

Abstract

Background Adult-onset Still's disease (AOSD) is a systemic inflammatory condition characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. The inflammatory status of AOSD could result from a deregulation of the NLRP3 inflammasome as Interleukin-1 (IL-1) is pivotal in the pathogenesis of AOSD.

Objectives To evaluate IL-1 beta and caspase-1 p45 expression in AOSD patients.

Methods 11 AOSD patients with systemic chronic disease (mean age: 44.5±15.6 years; mean disease duration: 3.0±1.7 years) and 5 healthy donors (mean age: 41.8±7.5) were enrolled. Anakinra (in 6 patients) and DMARDs (in 5 patients) adequately controlled the disease. PBMCs (peripheral blood mononuclear cells) obtained by Ficoll centrifugation were stimulated with lipopolysaccharide (LPS) [10 ng/ml] and ATP [1 mM] for 0.5, 1, 6 and 24 hours. IL-1β level was measured in the supernatant by ELISA and the expression of caspase-1 p45 at protein level was detected by Western Blotting.

Results In unstimulated PBMCs minimal IL-1β production was found both in AOSD patients and controls. After 6 hours stimulation, IL-1β level was increased whereas we observed a reduced processing of caspase-1 p45 particularly in AOSD patients treated with Anakinra.

Figure 1.

IL-1β secretion and caspase-1 p45 intracellular expression: differences between stimulated and unstimulated PMBCs in anakinra and DMARDs treated AOSD patients and in healthy controls.

Conclusions Patients with refractory AOSD, who therefore need Anakinra, seem to have an increased production of IL-1β compared to healthy controls and to AOSD patients who respond to standard therapies. Altered processing of caspase-1 p45 in AOSD patients support the involvement of the NLRP3 inflammasome pathway in the pathogenesis of the disease.

Disclosure of Interest None declared

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