Sickle cell vaso-occlusion causes activation of iNKT cells that is decreased by the adenosine A2A receptor agonist regadenoson. Blood 2013 Apr 25;121(17):3329-34
Date
02/05/2013Pubmed ID
23377438Pubmed Central ID
PMC3637009DOI
10.1182/blood-2012-11-465963Scopus ID
2-s2.0-84879350342 (requires institutional sign-in at Scopus site) 80 CitationsAbstract
Adenosine A2A receptor (A2AR) agonists reduce invariant natural killer T (iNKT) cell activation and decrease inflammation in sickle cell disease (SCD) mice. We conducted a phase 1 trial of the A2AR agonist regadenoson in adults with SCD. The target dose was 1.44 μg/kg/h. iNKT cell activation was evaluated using antibodies targeting the p65 subunit of nuclear factor-κB (phospho-NF-κB p65), interferon-γ (IFN-γ), and A2AR. Regadenoson was administered to 27 adults with SCD. We examined 21 patients at steady state and 6 during painful vaso-occlusive crises (pVOC). iNKT cell activation was also measured in 14 African-American controls. During pVOC, the fraction of iNKT cells demonstrating increased phospho-NF-κB p65 and A2AR expression was significantly higher compared with controls (P < .01) and steady-state patients (P < .05). IFN-γ expression was also significantly higher compared with controls (P = .02). After a 24-hour infusion of regadenoson during pVOC, phospho-NF-κB p65 activation in iNKT cells decreased compared to baseline by a median of 48% (P = .03) to levels similar to controls and steady-state SCD. No toxicities were identified. Infusional regadenoson administered to adults with SCD at 1.44 μg/kg/h during pVOC decreases activation of iNKT cells without toxicity.
Author List
Field JJ, Lin G, Okam MM, Majerus E, Keefer J, Onyekwere O, Ross A, Campigotto F, Neuberg D, Linden J, Nathan DGAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine A2 Receptor AgonistsAdult
Anemia, Sickle Cell
Case-Control Studies
Female
Flow Cytometry
Humans
Infusions, Intravenous
Interferon-gamma
Male
Natural Killer T-Cells
Phosphorylation
Prognosis
Purines
Pyrazoles
Receptor, Adenosine A2A
Tissue Distribution
Transcription Factor RelA
Vascular Diseases
