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

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.
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.
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.
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).
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.
AuthorsS Yoshida, H Sakamoto, Y Yamawaki, T Shoji, K Akahori, K Onuma, H Nakagawa, H Hasegawa, H Amayasu
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 102 Issue 6 Pt 1 Pg. 909-14 (Dec 1998) ISSN: 0091-6749 [Print] UNITED STATES
PMID9847430 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Asthmatic Agents
  • Leukotriene E4
  • Aspirin
  • Acyclovir
  • Acyclovir (administration & dosage, pharmacology)
  • Administration, Oral
  • Adult
  • Anti-Asthmatic Agents (administration & dosage, pharmacology)
  • Aspirin (adverse effects)
  • Asthma (chemically induced, physiopathology, prevention & control)
  • Bronchoconstriction (drug effects)
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume (drug effects)
  • Humans
  • Leukotriene E4 (urine)
  • Male
  • Middle Aged
  • Vital Capacity (drug effects)

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