title: Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10-producing T cells and increased lamina propria plasmacytoid dendritic cells.
abstract: Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 microg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4(+) memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123(+) plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-gamma production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa.
authors.affiliation: Mucosal Immunity Section, Laboratory of Host Defense, NIAID, NIH, Bethesda, MD, USA. pmannon@uab.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Mannon
authors.forename: F
authors.initials: F
authors.lastname: Leon
authors.forename: I J
authors.initials: IJ
authors.lastname: Fuss
authors.forename: B A
authors.initials: BA
authors.lastname: Walter
authors.forename: M
authors.initials: M
authors.lastname: Begnami
authors.forename: M
authors.initials: M
authors.lastname: Quezado
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Yi
authors.forename: C
authors.initials: C
authors.lastname: Groden
authors.forename: J
authors.initials: J
authors.lastname: Friend
authors.forename: R L
authors.initials: RL
authors.lastname: Hornung
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Gurprasad
authors.forename: B
authors.initials: B
authors.lastname: Kelsall
authors.forename: W
authors.initials: W
authors.lastname: Strober
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009092:Mucous Membrane / Q000276:immunology; D010865:Pilot Projects; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor