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

Abstract

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.

• Authors: S Yoshida, H Sakamoto, Y Yamawaki, T Shoji, K Akahori, K Onuma, H Nakagawa, H Hasegawa, H Amayasu
• Journal: The 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
• PMID: 9847430 (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)