Eicosanoids in drug allergy
Most of the information available on the role of eicosanoids in allergy
and related diseases concerns NERD.187,188 This fact
can be explained because it was the first clinical phenotype in which a
link between NSAIDs pharmacological activity and the inhibition of
PGE2 synthesis by blocking COX-1 and the subsequent
increase in cysteinyl-LTs release was established.189Nevertheless, some data are also available for cutaneous NSAID-induced
cross-hypersensitivity. Thus, increased LTE4 and
9α,11β-PGF2 urinary levels have been described for
NERD190-193 and for NSAID-induced acute
urticaria/angioedema (NIUA).193
For NSAID-exacerbated cutaneous disease (NECD), contrasting results have
been found regarding eicosanoids levels at basal state. Thus, Di Lorenzoet al . did not report baseline differences for
LTE4 in patients with chronic urticaria and
hypersensitivity to acetylsalicylic acid (ASA, aspirin) or food
additives,194 and no variations at basal state were
reported for LTE4 and 9α,11β-PGF2 by two
other independent studies.191,193 However, Mastalerzet al . reported increased LTE4 levels in NECD
patients with a positive aspirin challenge with respect to those with a
negative aspirin challenge, and with no changes found for
9α,11β-PGF2.195 It has been recently
published that NIUA and NECD showed similar increased levels in both
LTE4 and 9a,11b-PGF2 within the first 3
hours following a positive aspirin challenge; however, after this time
interval these mediators showed different behaviours, being such levels
long-lasting in NECD.193 In spite of these differences
being not statistically significant, the reasons explaining the
existence of these particular profiles are at present unknown although
they may be due to the presence of additional factors in NECD, which
could include sensitization to autoantibodies or the existence of
histamine-releasing factors.193
Data on the role of eicosanoids beyond NSAIDs-hypersensitivity are
scarce. However, a potential role for cysteinyl-LTs was proposed in
adverse reactions to non-ionic contrast media. Thus, iopromide and
iotrolan induced a significant increase of cysteinyl-LTs in vivo ,
with no changes in preformed mediators levels.196However, a previous study showed the heterogeneity of the effects of
contrast media on mediator release, showing an increase in histamine and
tryptase release from different human cells without changes in
LTE4 or PGD2levels.197