Effects of dexamethasone on leukotriene synthesis and airway responses to antigen and leukotriene D4 in rats.
Cysteinyl-leukotrienes (cysteinyl-LTs) are important mediators of both early and late allergen-induced airway responses in atopic asthmatics. We have investigated the effects of glucocorticoids on the in vivo synthesis of cysteinyl-LTs and airway responses to these mediators. Ovalbumin (OA)-sensitized Brown Norway rats, which exhibit early responses and, in most cases, also late responses to late antigen challenge, were treated with either one dose (1 h before antigen challenge) or two doses (2 and 14 h before challenge) of dexamethasone (dex; 300 micrograms/kg). A third group of sensitized rats which did not receive dex served as control animals. All rats were subjected to bile duct cannulation and tracheal intubation 2 h before intratracheal instillation of OA. All of the OA-treated control rats had pronounced early responses (5.5 +/- 1.0 times baseline pulmonary resistance [RL]), whereas 5 of 7 rats had late responses. Biliary levels of N-acetyl-LTE4 increased in all control rats following antigen challenge with a maximum occurring between 1 to 2 h, followed by a decline. There appeared to be a second maximum between 6 to 7 h after challenge, although this could not be demonstrated statistically because of the variability in the response among animals. Treatment with two doses of dex reduced the early response by 57%, completely eliminated the late response, and reduced the levels of N-acetyl-LTE4 in bile by about 80% at all time points.(ABSTRACT TRUNCATED AT 250 WORDS)
Powell
W S
WS
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Xu
L J
LJ
Martin
J G
JG
D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001985:Bronchial Provocation Tests; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D015289:Leukotrienes; D017998:Leukotriene D4; D003907:Dexamethasone