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Published on: April 13, 2010
Effect of acyclovir on bronchoconstriction and urinary leukotriene E4 excretion in aspirin-induced asthma
S Yoshida1, H Sakamoto, Y Yamawaki
1Institute for Medical Sciences, Fujita Health University School of Medicine, Toyoake, Japan.
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 E4 (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.
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