Nasal secretion in ragweed-sensitized dogs: effect of leukotriene synthesis inhibition.
Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.
Cardell
L O
LO
Cardiovascular Research Institute and the Department of Medicine, University of California at San Francisco, USA. Lars-Olaf.Cardell@oron.mas.lu.se
Agustí
C
C
Nadel
J A
JA
D000818:Animals; D004285:Dogs; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D006967:Hypersensitivity / Q000209:etiology*; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009297:Nasal Mucosa / Q000378:metabolism*; D015508:Nasal Obstruction / Q000503:physiopathology*; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010944:Plants; D011058:Pollen / Q000009:adverse effects*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors
D020024:Leukotriene Antagonists; D007975:Leukotriene B4; C063449:zileuton; D006918:Hydroxyurea