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