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

AbstractBACKGROUND:
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.
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
Topics
  • 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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