INTRANASAL SALMETEROL INHIBITS ALLERGEN-INDUCED VASCULAR-PERMEABILITYBUT NOT MAST-CELL ACTIVATION OR CELLULAR INFILTRATION

Background Salmeterol is a long-acting beta(2)-adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non-bronchodilator actions of salmeterol may contribute to its effica cy. Objective To further evaluate the potential non-bronchodilator act ions of salmeterol in vivo, using a model of nasal challenge with alle rgen. Methods Twelve asymptomatic subjects with seasonal allergic rhin itis participated in a randomized, double-blind, placebo-controlled cr ossover trial of the effects of a single dose of 100 mu g of salmetero l on the response to allergen challenge. Sneezing and symptom scores, and levels of histamine and albumin in nasal lavages, were measured th roughout the protocol. Concentrations of tryptase, prostaglandin D-2 a nd lysozyme were measured during the acute allergic response, while le vels of IL-3, IL-5 and IL-8 were measured at later time points. Number s of eosinophils and of total white blood cells were also recorded. Re sults Salmeterol did not affect sneezing or symptom scores at any poin t. During the immediate response to allergen challenge, mast cell acti vation, reflected by concentrations of histamine, tryptase and prostag landin D-2, and serous glandular secretion, assessed by measurements o f lysozyme, were unaffected by salmeterol treatment but vascular perme ability, reflected by concentrations of albumin in nasal lavages, was significantly reduced. At later time points, salmeterol had no effect on levels of histamine or albumin and did not affect cellular infiltra tion. Concentrations of IL-3, IL-5 and IL-8 were not increased by alle rgen challenge in these subjects, so the effects of salmeterol could n ot be evaluated. Conclusions Treatment with a single dose of salmetero l had no effect on activation of mast cells or cellular infiltration b ut inhibited vascular permeability. The ability of salmeterol to inhib it antigen-induced vascular permeability may contribute to Its therape utic efficacy in asthma.