title: Cladribine exerts an immunomodulatory effect on human and murine dendritic cells.
abstract: 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-γ- and tumor necrosis factor-α-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.
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Stefan H P
authors: SH
authors: Kraus
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. Electronic address: luessi@uni-mainz.de.
authors: Felix
authors: F
authors: Luessi
authors: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Bettina
authors: B
authors: Trinschek
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Steffen
authors: S
authors: Lerch
authors: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Mario
authors: M
authors: Hubo
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Laura
authors: L
authors: Poisa-Beiro
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Magdalena
authors: M
authors: Paterka
authors: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Helmut
authors: H
authors: Jonuleit
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Frauke
authors: F
authors: Zipp
authors: Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors: Valérie
authors: V
authors: Jolivel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis; D017338:Cladribine / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003911:Dextrans / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D003911:Dextrans; D007155:Immunologic Factors; C015219:fluorescein isothiocyanate dextran; D017338:Cladribine; D016650:Fluorescein-5-isothiocyanate
keywords: APC; CFSE; CNS; CSF; Cladribine; DC; Dendritic cell; EAE; Immunomodulation; MLR; MS; PBMC; PI; antigen presenting cells; carboxyfluorescein succinimidyl ester; central nervous system; cerebrospinal fluid; dendritic cells; experimental autoimmune encephalomyelitis; mAb; mixed leukocyte reaction; monoclonal antibody; multiple sclerosis; peripheral blood mononuclear cells; propidium iodide