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


CONCLUSIONS
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.
Yoshida
S
S
Institute for Medical Sciences, Fujita Health University School of Medicine, Toyoake, Japan.
Sakamoto
H
H
Yamawaki
Y
Y
Shoji
T
T
Akahori
K
K
Onuma
K
K
Nakagawa
H
H
Hasegawa
H
H
Amayasu
H
H
D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D014797:Vital Capacity / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D017999:Leukotriene E4; D001241:Aspirin; D000212:Acyclovir