Inhaled budesonide inhibits OVA-induced airway narrowing, inflammation, and cys-LT synthesis in BN rats.
The objective of the present investigation was to examine the effects of an inhaled glucocorticoid, budesonide, on antigen-induced production of cysteinyl leukotrienes (cys-LTs) and pulmonary inflammatory cell infiltration in the Brown Norway rat, an animal model of asthma. Two weeks after sensitization to ovalbumin, rats were treated with budesonide (2.5 mg/kg) 18 and 1 h before challenge with antigen. Budesonide abolished the late response to ovalbumin (P<0.02) and strongly inhibited the in vivo synthesis of N-acetyl-leukotriene E(4), an indicator of cys-LT synthesis, during this period (P<0.005). Both total bronchoalveolar lavage (BAL) cells (P<0.01) and BAL macrophages (P<0.005) were markedly reduced to approximately 25% of their control levels after treatment with budesonide. It can be concluded that inhibition of the antigen-induced late response in Brown Norway rats by budesonide is associated with reductions in both BAL macrophages and cys-LT synthesis. It is possible that the effect of budesonide on cys-LT synthesis is related to its effects on pulmonary macrophages.
Xu
L
L
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H2X 2P2.
Olivenstein
R
R
Martin
J G
JG
Powell
W S
WS
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D003545:Cysteine / Q000378:metabolism; D017999:Leukotriene E4 / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN
D001993:Bronchodilator Agents; D019819:Budesonide; D017999:Leukotriene E4; C047630:N-acetylleukotriene E4; D010047:Ovalbumin; D003545:Cysteine