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Clin Exp Immunol. 2016 Mar;183(3):350-7. doi: 10.1111/cei.12731. Epub 2015 Dec 7.

Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.

Author information

1
Departments of Pediatric Endocrinology, University of Florida, Gainesville, FL, USA.
2
Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
3
Biomedical Engineering, University of Florida, Gainesville, FL, USA.
4
Health Outcomes and Policy, University of Florida, Gainesville, FL, USA.

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.

KEYWORDS:

clinical trial; granulocyte-colony stimulating factor; human; monotherapy; type 1 diabetes

PMID:
26462724
PMCID:
PMC4750600
[Available on 2017-03-01]
DOI:
10.1111/cei.12731
[Indexed for MEDLINE]
Free PMC Article

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