title: Effects of clozapine on hematopoiesis and the cytokine system.
abstract: Using a bioassay for hematopoietic progenitor cells we looked for mechanisms causing clozapine induced neutropenia and agranulocytosis. Micro-agar-cultures of normal peripheral blood mononuclear cells (MNC) of eight patients currently treated with clozapine and of eight probands not receiving any kind of pharmacological treatment were incubated with increasing concentrations of clozapine (0, 7.5, 15, 30 micrograms/ml). Erythropoiesis and megakaryopoiesis were totally unaffected by clozapine. A biologically relevant suppression of granulopoiesis (CFU-GM) could only be shown in cultures incubated with 30 micrograms/ml clozapine. Cytokine analysis presented a strictly dose-dependent suppression of GM-CSF and neopterin release in all cultures. There was no difference between patients and controls at any clozapine concentration. The data support a possible role for cytokines as one mediator of the agranulocytosis producing effects of clozapine.
authors.affiliation: Department of Psychiatry, Innsbruck University Clinics, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Sperner-Unterweger
authors.forename: S
authors.initials: S
authors.lastname: Gaggl
authors.forename: W W
authors.initials: WW
authors.lastname: Fleischhacker
authors.forename: C
authors.initials: C
authors.lastname: Barnas
authors.forename: M
authors.initials: M
authors.lastname: Herold
authors.forename: D
authors.initials: D
authors.lastname: Geissler
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D002478:Cells, Cultured; D003024:Clozapine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D019798:Neopterin
chemical_list: D001708:Biopterins; D019798:Neopterin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003024:Clozapine