Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 18, Issue 2, Pages 347-357Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2013.11.027
Keywords
Dendritic cell; Cladribine; Immunomodulation
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Funding
- German Research Foundation [SFB-TR 128/B4]
- MAIFOR-grant of the Johannes Gutenberg-University Mainz
- Merck Serono GmbH
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Cladribine is a purine nucleoside analog developed to treat lymphoid malignancies. Reported therapeutic benefits for the autoimmune disease multiple sclerosis indicate additional immunomodulatory effects beyond the well-characterized cytotoxic activity causing lymphopenia. Here, we demonstrate that cladribine reduces the secretion of inflammatory cytokines and chemokines by murine and human dendritic cells, the most potent antigen-presenting cells. This compound also modulates the expression of the activation markers CD86 and MHC II. Furthermore, cladribine affects the T cell priming capacity of dendritic cells, resulting in reduced induction of interferon-gamma- and tumor necrosis factor-alpha-producing T cells and increased induction of interleukin-10-producing T cells. These effects, observed at cladribine concentrations in the therapeutically relevant range of serum steady-state concentrations for leukemia and multiple sclerosis, confirm the immunomodulatory activity of cladribine. (C) 2013 Elsevier B.V. All rights reserved.
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