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.
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| 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.
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| Authors | P J Mannon, F Leon, I J Fuss, B A Walter, M Begnami, M Quezado, Z Yang, C Yi, C Groden, J Friend, R L Hornung, M Brown, S Gurprasad, B Kelsall, W Strober |
| Journal | Clinical and experimental immunology (Clin Exp Immunol) Vol. 155 Issue 3 Pg. 447-56 (Mar 2009) ISSN: 1365-2249 [Electronic] England |
| PMID | 19094118 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural) |
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