title: Procaterol potentiates the anti-inflammatory activity of budesonide on eosinophil adhesion to lung fibroblasts.
abstract: BACKGROUND
  The interaction between leukocytes and various parenchymal cells is the first step of inflammation. Therefore, the adhesion of eosinophils to lung fibroblasts is thought to be a crucial step in the inflammatory process of asthma. Procaterol, a beta(2)-selective full agonist, is currently prescribed for patients with asthma. In addition to its potent bronchodilatory action, the agonist has been reported to have anti-inflammatory actions. In this study, to examine whether procaterol can potentiate the anti-inflammatory action of glucocorticoids, the effect of procaterol on eosinophil adhesion to normal human lung fibroblasts (NHLF) was assessed in the presence and absence of budesonide, one of the most potent glucocorticoids.
  
  
  METHODS
  Following pretreatment of NHLF with tumor necrosis factor-alpha (TNF-alpha) in the presence of various concentrations of procaterol and/or budesonide, the eotaxin-stimulated eosinophil adhesion was determined using the peroxidase activity of eosinophils. To investigate the mechanism of the inhibitory action of procaterol, TNF-alpha-induced expression of adhesion molecules, ICAM-1 and VCAM-1, in NHLF was also evaluated.
  
  
  RESULTS
  Pretreatment with procaterol inhibited the adhesion of eosinophils to NHLF in a concentration-dependent manner, and shifted the concentration-response curve of budesonide to the left. Both procaterol and budesonide resulted in concentration-dependent inhibition of expression of ICAM-1 and VCAM-1 in NHLF, and an additive inhibitory effect was found when the agents were combined.
  
  
  CONCLUSIONS
  Given the results of this study which indicated that procaterol exerted an additive action on the anti-inflammatory effect of budesonide, procaterol and glucocorticoids may provide better control for asthma when used together than when used separately.
authors: Free Radical Project, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan. n_yoshida@research.otsuka.co.jp
authors: Norihiro
authors: N
authors: Yoshida
authors: Masahiro
authors: M
authors: Muraguchi
authors: Masayuki
authors: M
authors: Kamata
authors: Katsumi
authors: K
authors: Ikezono
authors: Toyoki
authors: T
authors: Mori
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019819:Budesonide / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D054413:Chemokine CCL11 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000473:pathology; D017265:Procaterol / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054413:Chemokine CCL11; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D017265:Procaterol