Aspirin Intolerance: Experimental Models for Bed-to-Bench

Yamashita, Masamichi

We have tried to develop a cellular model of AERD based on inhibition PG production by NSAIDs, and we pre-viously assessed the effect on cysLT production in the RBL-2H3 mast cell line derived from rat basophilic leukemia [56] . We choose indomethacin (≦3 µM, Fig. 1b) as the NSAID to avoid unexpected protein acetylation by using aspirin [57] . We found that cysLT production increased when RBL-2H3 cells were pretreated overnight with dinitrophenol (DNP)specific immunoglobulin E (IgE) and then treated with DNPconjugated human serum albumin, creating a cellular model of type I allergy [58] [59] [60] . Treatment with indomethacin at concentration up to 3 μM did not cause dose-dependent changes of cysLT production, while there was almost 90% inhibition of PGD 2 production. LTB 4 production was significantly increased by indomethacin at 1-3 μM. Our observation regarding LTB 4 is supported by a study of Planaguma et al. [61] using rat Kupffer cells; adding aspirin (up to 5 mM) doubled LTB 4 production while inhibiting PGE 2 production approximately 60%. Then we tried adding arachidonic acid (1-10 μM) with DNP-HSA to the culture medium of RBL-2H3 cells. Cysteinyl LT production was significantly increased by adding arachidonic acid combined with allergic stimulation, while there was no significant change without allergic stimulation [57] .