Urinary LTE4 excretion in antigen-provoked asthmatic patients treated with the inhaled LTD4 antagonist, L-648,051.
Leukotriene (LT) E4 represents the major LT metabolite in man, and its urinary excretion can be used as an indirect marker of systemic LTC4 and/or LTD4 synthesis and release. In the present study LTE4 excretion was monitored for 24 h in 12 atopic patients with mild asthma undergoing antigen bronchoprovocation as part of a double-blind, placebo-controlled, two-period cross-over study of the aerosol-delivered LTD4 antagonist, L-648,051. Urinary LTE4 excretion was also studied separately in six of the patients after inhaling only diluent. Urine was sampled before, and serially after antigen challenge, at intervals corresponding to the immediate (0-3 h postchallenge) and late (3-6, 6-12, 12-24 h postchallenge) asthmatic reactions. LTE4 was determined by reversed-phase HPLC and radioimmunoassay. Forced expiratory volume in 1 s (FEV1) was recorded serially through 8 h after inhalation of antigen and diluent. Compared to base-line measurements, antigen bronchoprovocation induced significant increases in mean LTE4 excretion rates 0-3 h postchallenge (i.e. during the immediate asthmatic response) after treatment with both placebo (P < 0.01) and L-648,051 (P < 0.05). These mean LTE4 excretion rates in the immediate phase were also significantly higher than the mean rates in the late phase (3-6 h and beyond); the excretion rates of LTE4 at these later time intervals were similar to base-line values. After inhalation of diluent, the LTE4 excretion rates in the intervals 0-3, 3-6, 6-12 and 12-24 h were unchanged from base-line values.(ABSTRACT TRUNCATED AT 250 WORDS)
Rasmussen
J B
JB
Department of Pulmonary Medicine, University of Lund, Malmö General Hospital, Sweden.
Eriksson
L O
LO
Tagari
P
P
Margolskee
D J
DJ
Girard
Y
Y
Andersson
K E
KE
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D007651:Keto Acids / Q000627:therapeutic use*; D017999:Leukotriene E4; D008297:Male; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine; D013450:Sulfones / Q000627:therapeutic use*
D007651:Keto Acids; D013189:SRS-A; D013450:Sulfones; D017999:Leukotriene E4; C052024:L 648051