Title:Aspirin Intolerance: Experimental Models for Bed-to-Bench
VOLUME: 17 ISSUE: 16
Author(s):Masamichi Yamashita
Affiliation:Laboratory of Food for Health, Department of Bioscience in Daily Life, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880 Japan.
Keywords:Arachidonic acid metabolism, aspirin intolerance, aspirin-exacerbated respiratory disease, aspirin-induced urticaria,
cysteinyl leukotrienes, food-dependent exercise-induced anaphylaxis, prostaglandins, mast cells.
Abstract:Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it
sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory
disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance)
are also observed in patients with food-dependent exercise-induced anaphylaxis,
a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and
the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular
model of AERD, because its pathophysiological mechanism is still unknown, but
it is thought that inhibition of cyclooxygenase by causative agents leads to an increase
of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs)
that provoke airway smooth muscle constriction and asthma symptoms. As the bed-tobench
approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop
a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin
(another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3
cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since
this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should
respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent
bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for
development of in vitro AERD models as the approach from bench-to-bed.
