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.
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.
Mannon
P J
PJ
Mucosal Immunity Section, Laboratory of Host Defense, NIAID, NIH, Bethesda, MD, USA. pmannon@uab.edu
Leon
F
F
Fuss
I J
IJ
Walter
B A
BA
Begnami
M
M
Quezado
M
M
Yang
Z
Z
Yi
C
C
Groden
C
C
Friend
J
J
Hornung
R L
RL
Brown
M
M
Gurprasad
S
S
Kelsall
B
B
Strober
W
W
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
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor