title: Myeloid cells as target of fingolimod action in multiple sclerosis.
abstract: OBJECTIVE
  To track the effects of fingolimod, an approved drug for multiple sclerosis (MS), on the activation of myeloid cells from the periphery to the CNS.
  
  
  METHODS
  In vitro and ex vivo immunologic studies coupled with flow cytometry were performed to evaluate the action of fingolimod on lipopolysaccharide (LPS)-induced expression of activation markers in human monocytes from healthy participants, participants with untreated MS, and participants with fingolimod-treated MS. In vivo administration of fingolimod during experimental autoimmune encephalomyelitis (EAE) was established to verify the activation state of splenic, CNS infiltrating, and CNS resident myeloid cells ex vivo at flow cytometer.
  
  
  RESULTS
  We found that in vitro exposure of human monocytes to fingolimod inhibited LPS-induced CD25 and CD150 expression and tumor necrosis factor-α (TNF-α) secretion without altering immune cell survival. Further, EAE treatment with fingolimod led to reduced amounts of TNF-α produced by myeloid cells in vivo in the spleen and CNS. Finally, while displaying normal induction of CD25 and CD150 levels at high LPS concentration, monocytes from patients with fingolimod-treated MS showed significantly higher activation threshold at suboptimal LPS stimulation than controls.
  
  
  CONCLUSIONS
  The inhibition of myeloid cell activation may be part of the immunosuppressive action of fingolimod and take place in the periphery and in the CNS.
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Dario
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Govi
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: De Feo
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Messina
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Romeo
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sangalli
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Moiola
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Mariaemma
authors.initials: M
authors.lastname: Rodegher
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cinthia
authors.initials: C
authors.lastname: Farina