title: Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin-induced asthma to threshold dose of aspirin.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawano
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsuse
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Ikuko
authors.initials: I
authors.lastname: Machida
authors.forename: Sachiko
authors.initials: S
authors.lastname: Saeki
authors.forename: Shinya
authors.initials: S
authors.lastname: Tomari
authors.forename: Kazuko
authors.initials: K
authors.lastname: Mitsuta
authors.forename: Chizu
authors.initials: C
authors.lastname: Fukushima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.forename: Terufumi
authors.initials: T
authors.lastname: Shimoda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: 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*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; D017999:Leukotriene E4; D047150:Eosinophil Cationic Protein; D001241:Aspirin; D016559:Tacrolimus