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Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity

2011; Elsevier BV; Volume: 240-241; Linguagem: Inglês

10.1016/j.jneuroim.2011.09.010

1872-8421

Bruno Laugel, Frédéric Borlat, Laurent Galibert, Alain Vicari, Robert Weissert, Yolande Chvatchko, Denis Bruniquel,

Acute Lymphoblastic Leukemia research

Cladribine (2-chloro-2'-deoxyadenosine) is a purine nucleoside analogue (PNA) which causes targeted and sustained reduction of peripheral lymphocyte counts. Cladribine tablets produced significant treatment benefit for patients with relapsing-remitting multiple sclerosis in the phase 3 CLARITY study. In addition to the well-characterised cell-specific phosphorylation of PNAs responsible for lymphocyte reduction, the mode of action of cladribine may encompass distinct activities contributing to its overall effects on the immune system. Here we demonstrate that clinically relevant concentrations of cladribine also inhibit cytokine secretion by human peripheral blood T cells in vitro through mechanisms independent of the induction of lymphocyte death.