title: Allometric dose retranslation unveiled substantial immunological side effects of granulocyte colony-stimulating factor after stroke.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (GCSF) showed robust neuroprotective and neuroregenerative properties after stroke in rodents but failed to meet study end points in patients. Because immunologic side effects of GCSF may have escaped preclinical testing because of nonallometric dose translation, we hypothesized those as possible reasons.
  
  
  METHODS
  Stroke was induced in C57BL/6 mice by 45-minute filament middle cerebral artery occlusion. GCSF was administered at 50 and 832.5 μg/kg body weight. Treatment was controlled by vehicle injection, sham surgery, and naive animals. Immune cell counts were assessed in blood, spleen, and brain by multidimensional flow cytometry 1 day after stroke.
  
  
  RESULTS
  High-dose GCSF significantly altered myeloid and T-cell subpopulations in blood and spleen and caused a tremendous increase of monocytes/macrophages infiltrating the ischemic brain.
  
  
  CONCLUSIONS
  Dose-dependent immunomodulation superimposes central nervous system-specific effects of GCSF after stroke. Adaption of dose or treatment time may overcome this drawback.
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (D.-C.W., C.P., I.S., G.S., J.B., F.L., J.S., K.M., G.W.); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany (D.-C.W., J.B., G.W.); and Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA (J.B.).
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
authors.forename: Claudia
authors.initials: C
authors.lastname: Pösel
authors.forename: Isabell
authors.initials: I
authors.lastname: Schulz
authors.forename: Gerda
authors.initials: G
authors.lastname: Schicht
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.forename: Franziska
authors.initials: F
authors.lastname: Lange
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheibe
authors.forename: Karoline
authors.initials: K
authors.lastname: Möller
authors.forename: Gesa
authors.initials: G
authors.lastname: Weise
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D056747:Immunomodulation; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010525:Peripheral Nerves / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000473:pathology; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: granulocyte colony–stimulating factor; immune system; stroke