Effect of acyclovir on bronchoconstriction and urinary leukotriene E4 excretion in aspirin-induced asthma

[摘要] Background: Acyclovir (9-[2-hydroxyethoxymethyl] guanine), an inhibitor of the DNA polymerase of the herpes virus, has been reported to exhibit pharmacologic activity other than antiviral activity, including antiasthmatic effects. Objective: This study was designed to investigate the protective effect of acyclovir on airway responsiveness to the sulpyrine provocation test and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary leukotriene E-4 (u-LTE4), a marker of cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. Methods: We assessed the effects of pretreatment with acyclovir on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate aspirin-induced asthma; those who were in stable clinical condition and were hyperresponsive to the sulpyrine provocation test were allocated to this study. A double-blind, randomized, cross-over design was used, u-LTE4 was measured by a combined reverse-phase HPLC enzyme immunoassay. Results: Acyclovir protects against aspirin-induced attacks of asthma through mechanisms unrelated to its bronchodilator property but related to the improvement of bronchial hypersensitivity to sulpyrine; protection was nearly complete in all patients (P < .0001). By contrast, after acyclovir, the maximum Level of u-LTE4 in patients was significantly lower than that in control subjects (P < .01). Conclusion: Our results suggest that acyclovir is not only an antiviral drug but also an inhibitor of analgesic-induced bronchoconstriction, probably acting by inhibiting the release of. cysteinyl LTs.

[发布日期] 1998-12-01

[关键词] acyclovir;aspirin-induced asthma;cyclooxygenase;leukotriene