Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin-induced asthma to threshold dose of aspirin.
BACKGROUND
The exact mechanism of aspirin-induced asthma is not clear. It has been postulated that precipitation of asthma attacks by aspirin is linked to inhibition of COX activity and massive release of cysteinyl leukotriene into the airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for immunosuppression in organ transplantation and also for allergic diseases such as atopic dermatitis.


OBJECTIVE
We evaluated the effects of tacrolimus in aspirin-induced asthma by using a double-blind, crossover study design.


METHODS
Twelve patients with aspirin-induced asthma (male:female, 3:9; mean age +/- SD, 36.7 +/- 7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the threshold dose of oral aspirin.


RESULTS
In the placebo arm, oral aspirin significantly decreased FEV 1 concomitant with significant increases in sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. Tacrolimus significantly inhibited bronchoconstriction and abrogated aspirin-induced increase in both sputum eosinophilic cationic protein and urinary leukotriene E(4) levels.


CONCLUSIONS
The current study suggested that tacrolimus inhibited bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl leukotriene excretion.
Kawano
Tetsuya
T
Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
Hiroto
H
Kondo
Yuki
Y
Machida
Ikuko
I
Saeki
Sachiko
S
Tomari
Shinya
S
Mitsuta
Kazuko
K
Fukushima
Chizu
C
Obase
Yasushi
Y
Shimoda
Terufumi
T
Kohno
Shigeru
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology; D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; D017999:Leukotriene E4; D047150:Eosinophil Cationic Protein; D001241:Aspirin; D016559:Tacrolimus