Salmeterol inhibits anaphylactic histamine release from guinea-pig isolated mast cells

Abstract

Salmeterol (1 nM-100 microM) showed an inhibitory action on anaphylactic histamine release from mast cells, isolated from pleural and peritoneal cavities of actively sensitized guinea-pigs and stimulated by incubation with allergen. The effect is concentration-dependent and is reduced by the beta-adrenoceptor antagonist propranolol (1 microM). This study supports the hypothesis of an anti-inflammatory property of salmeterol, which concerns cells involved in the early phases of asthma.

Effects of inhibitors of phosphodiesterase, on antigen‐induced bronchial hyperreactivity in conscious sensitized guinea‐pigs and airway leukocyte infiltration

“…As mentioned above, T‐lymphocytes are capable of synthesizing and releasing a number of cytokines which induce and regulate leukocyte recruitment and it is possible that inhibition of PDE3 could regulate this in some way. Alternatively, initial mast cell de‐granulation, which has been demonstrated to be regulated by cyclic AMP (Frossard et al , 1981; Undem et al , 1988; Gentilini et al , 1993) could be directly responsible for neutrophil recruitment. Human mast cells have been shown to store IL‐8 and TNFα (Bradding et al , 1994; 1995) both of which are relevant to the recruitment of neutrophils.…”

Can β2‐adrenoceptor agonists, anticholinergic drugs, and theophylline contribute to the control of pulmonary inflammation and emphysema in COPD?

“…Similarly, salmeterol inhibits LPSinduced TNF-a secretion by THP-1 cells, a human monocytic cell line and TNF-a level in murine serum [28]. Additionally, salmeterol exhibits potent and persistent inhibition of anaphylactic mediator release from passively sensitized human lung tissue and from guinea-pig isolated mast cells via b 2 -adrenoceptor [31,32], suggesting a potential benefit of b 2 -adrenoceptor agonists in the asthma therapy. Additionally, salmeterol exhibits potent and persistent inhibition of anaphylactic mediator release from passively sensitized human lung tissue and from guinea-pig isolated mast cells via b 2 -adrenoceptor [31,32], suggesting a potential benefit of b 2 -adrenoceptor agonists in the asthma therapy.…”

“…A lipopolysaccharide (LPS)-induced tumor necrosis factor a (TNF-a) and granulocyte-macrophage colony-stimulating factor (GM-CSF) release from monocyte-derived macrophages can be significantly inhibited by formoterol or salmeterol [27]. Other studies on airway epithelial cells stimulated Albuterol Reduction in GM-CSF expression and production [169] Isoproterenol Inhibition of the release of RANTES [170] Formoterol Reduction in GM-CSF release [29] Rhinovirus Formoterol Suppression of production of CXCL8 and bFGF [171] TNF-a Formoterol, salmeterol Reduction in IL-8, GM-CSF and VEGF secretion [30] Lung myofibroblasts TNF-a Salmeterol Decrease in IL-6 release and nuclear translocation of NF-kB [172] Mast cells IgE Salbutamol Salmeterol Inhibition of TNF-a release [173] Salmeterol Reduction in histamine release [31] Alveolar macrophages Endotoxin Formoterol, salmeterol Reduction in TNF-a and GM-CSF release [174] Salbutamol Formoterol Reduction in superoxide anion O À 2 release and bacterial killing [22] NTHi by TNF-a also illustrate the anti-inflammatory activity of b 2 -adrenoceptor agonists such as formoterol and salmeterol through a reduction of interleukin 8 (IL-8), GM-CSF, and vascular endothelial growth factor (VEGF) secretion [29,30]. Other studies on airway epithelial cells stimulated Albuterol Reduction in GM-CSF expression and production [169] Isoproterenol Inhibition of the release of RANTES [170] Formoterol Reduction in GM-CSF release [29] Rhinovirus Formoterol Suppression of production of CXCL8 and bFGF [171] TNF-a Formoterol, salmeterol Reduction in IL-8, GM-CSF and VEGF secretion [30] Lung myofibroblasts TNF-a Salmeterol Decrease in IL-6 release and nuclear translocation of NF-kB [172] Mast cells IgE Salbutamol Salmeterol Inhibition of TNF-a release [173] Salmeterol Reduction in histamine release [31] Alveolar macrophages Endotoxin Formoterol, salmeterol Reduction in TNF-a and GM-CSF release [174] Salbutamol Formoterol Reduction in superoxide anion O À 2 release and bacterial killing [22] NTHi by TNF-a also illustrate the anti-inflammatory activity of b 2 -adrenoceptor agonists such as formoterol and salmeterol through a reduction of interleukin 8 (IL-8), GM-CSF, and vascular endothelial growth factor (VEGF) secretion [29,…”

“…Other studies on airway epithelial cells stimulated by TNF-a also illustrate the anti-inflammatory activity of b 2 -adrenoceptor agonists such as formoterol and salmeterol through a reduction of interleukin 8 (IL-8), GM-CSF, and vascular endothelial growth factor (VEGF) secretion [29,30]. Additionally, salmeterol exhibits potent and persistent inhibition of anaphylactic mediator release from passively sensitized human lung tissue and from guinea-pig isolated mast cells via b 2 -adrenoceptor [31,32], suggesting a potential benefit of b 2 -adrenoceptor agonists in the asthma therapy. Some of the anti-inflammatory effects mentioned above are reversed by b-blockers, indicating a b 2adrenoceptor-dependent mechanism [22,28].…”