title: Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells.
abstract: BACKGROUND
  Methylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels in a cluster headache bout are normalized after a course of high dose corticosteroids. Here we assess whether MPD suppresses interleukin-1β (IL-1β)- and prostaglandin E2 (PGE2)-induced CGRP release in a cell culture model of trigeminal ganglia cells, which could account for the preventive effect in migraine and cluster headache. Metoprolol﻿(MTP), a migraine preventive with a slow onset of action, was used for comparison.
  
  
  METHODS
  Primary cultures of rat trigeminal ganglia were stimulated for 24 h with 10 ng/ml IL-1β or for 4 h with 10 μM PGE2 following the exposure to 10 or 100 μM MPD or 100 nM or 10 µM MTP for 45 min or 24 h. CGRP was determined by using a commercial enzyme immunoassay.
  
  
  RESULTS
  MPD but not MTP blocked IL-1β-induced CGRP release from cultured trigeminal cells. PGE2-stimulated CGRP release from trigeminal ganglia cell culture was not affected by pre-stimulation whether with MPD or MTP.
  
  
  CONCLUSIONS
  MPD but not MTP suppresses cytokine (IL-1β)-induced CGRP release from trigeminal ganglia cells. We propose that blockade of cytokine mediated trigeminal activation may represent a potential mechanism of action that mediates the preventive effect of MTP on cluster headache and recurrent migraine attacks.
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. lars.neeb@charite.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Neeb
authors.affiliation: Department of Neuroradiology, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hellen
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Reuter
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects*; D002478:Cells, Cultured; D003027:Cluster Headache / Q000517:prevention & control*; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008790:Metoprolol / Q000494:pharmacology*; D008881:Migraine Disorders / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D005938:Glucocorticoids; D053583:Interleukin-1beta; D008790:Metoprolol; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D008775:Methylprednisolone
keywords: Calcitonin gene related peptide; Cluster headache; Interleukin-1β; Methylprednisolone; Metoprolol; Migraine; Prostaglandin E2; Trigeminal ganglia cells