Effect of salmeterol on polymorphonuclear leukocyte (PMNL) chemiluminescence In Vitro

Abstract

Although beta-agonists remain an important aspect of the treatment of asthma, their role has recently been questioned. Salmeterol has recently been developed as a beta-agonist with prolonged bronchodilator action. Using lucigenin-enhanced chemiluminescence, we have shown that salmeterol inhibits this aspect of phagocyte function in vitro in a concentration-dependent manner. However, salmeterol differs from classical beta 2-agonists in that at concentrations between 10(-5) and 10(-3) mol/L, its effects on phagocytes cannot be completely reversed by washing the cells or by propranolol. The effects on phagocytes may not therefore be explicable on the basis of beta-adrenergic mechanisms alone.

Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro

“…This contention is supported by observations that the inhibitory effects of salmeterol on oxidant production by activated neutrophils were insensitive to propranolol and almost completely eliminated by washing the cells. These observations confirm previous studies in which salmeterol has been reported to inhibit oxidant generation by FMLP-and opsonized zymosan-activated neutrophils by undefined, P2adrenoceptor-independent mechanisms (Ramage et al, 1993;Vardey et al, 1994).…”

“…This contention is supported by observations that the inhibitory effects of salmeterol on oxidant production by activated neutrophils were insensitive to propranolol and almost completely eliminated by washing the cells. These observations confirm previous studies in which salmeterol has been reported to inhibit oxidant generation by FMLP-and opsonized zymosan-activated neutrophils by undefined, P2-adrenoceptor-independent mechanisms (Ramage et al, 1993;Vardey et al, 1994). The inhibitory effects of salmeterol on neutrophil superoxide generation were dose-related and observed with all four stimuli of membrane-associated oxidative metabolism, the intensity of their pro-oxidative interactions with these cells being an apparent determinant of sensitivity to salmeterol.…”

“…These agents, particularly the long-acting f32-agonists, formoterol and salmeterol, have also been reported to inhibit both the early and late phases of allergen-induced bronchoconstriction and bronchial hyperresponsiveness in atopic asthmatic patients by anti-inflammatory mechanisms which are distinct from those involving fl2-adrenoceptors (Twentyman et al, 1990;Palmqvist et al, 1992). These activities seem to be directed at various types of inflammatory cell, such as eosinophils (Eda et al, 1993), macrophages (Baker & Fuller, 1990) and neutrophils (Ramage et al, 1993;Vardey et al, 1994), and may, at least in the case of salmeterol, enable reductions in the dose of inhaled corticosteroids (Greening et al, 1994). Although clinically important, little is known about the biochemical mechanisms of these f2-adrenoceptor-independent interactions of f2-agonists with inflammatory cells.…”

Comparison of Salmeterol with Placebo in Mild Asthma: Effect on Peripheral Blood Phagocyte Function and Cytokine Levels

“…While there is very little evidence that these agents modify disease in a clinical setting [1], conven tional short-acting P-agonists do have anti-inflammatory ef fects in vitro [2,3], Consequently it seemed possible that recently produced long-acting P-agonists such as salmete rol might have disease-modifying activity. We have demon strated that salmeterol alters phagocyte function in vitro [4], and others have shown that salmeterol inhibits both aller gen-induced mediator release and inflammatory cell migra tion [5,6]. However, there is only one report containing re sults suggestive of a clinical anti-inflammatory effect [7].…”