title: Inhibition of eosinophil activation mediated by a Toll-like receptor 7 ligand with a combination of procaterol and budesonide.
abstract: BACKGROUND
  Viral respiratory tract infections play an important role in the inception and exacerbation of asthma. Eosinophils, major effector cells in asthma, often accumulate in the airways during viral infections and are possibly activated by respiratory RNA viruses through Toll-like receptor (TLR) 7. We investigated the effect of a β(2)-agonist, i.e. procaterol, and a corticosteroid, i.e. budesonide, that are commonly used for viral-induced asthma, on TLR7 ligand-induced activation of eosinophils in vitro.
  
  
  METHODS
  Purified peripheral blood eosinophils were incubated with procaterol and/or budesonide and stimulated with a TLR7 ligand, i.e. R-837. Expression of CD11b was analyzed by flow cytometry. Superoxide generation was measured via the cytochrome C reduction method. IL-8 in the supernatants was assayed by ELISA.
  
  
  RESULTS
  Although procaterol or budesonide alone did not inhibit R-837-induced CD11b expression, combinations of the 2 drugs significantly inhibited CD11b. Likewise, the combinations significantly inhibited O(2)(-) generation at low concentrations. Budesonide significantly inhibited R-837-induced IL-8 production in a concentration-dependent manner, and procaterol potentiated inhibition by budesonide although single-agent procaterol had no effect.
  
  
  CONCLUSIONS
  A combination of procaterol and budesonide inhibits the TLR7-mediated effector function of eosinophils, indicating their possible anti-inflammatory effect for virus-induced asthma.
authors.affiliation: Institute for Clinical Research, Mie National Hospital, Tsu, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hiraguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanida
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nagao
authors.forename: Reiko
authors.initials: R
authors.lastname: Tokuda
authors.forename: Takao
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D004338:Drug Combinations; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D000077271:Imiquimod; D016209:Interleukin-8 / Q000378:metabolism; D017265:Procaterol / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists*
chemical_list: D000634:Aminoquinolines; D000998:Antiviral Agents; D039481:CD11b Antigen; D004338:Drug Combinations; C509295:ITGAM protein, human; D016209:Interleukin-8; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D013481:Superoxides; D019819:Budesonide; D000077271:Imiquimod; D017265:Procaterol