Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity.
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.
Merck Serono SA, Geneva Research Center, 9 Chemin des Mines, CH-1202, Genève, Switzerland.
Bruno
B
Laugel
Frédéric
F
Borlat
Laurent
L
Galibert
Alain
A
Vicari
Robert
R
Weissert
Yolande
Y
Chvatchko
Denis
D
Bruniquel
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D017338:Cladribine / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D017338:Cladribine; D003842:Deoxycytidine Kinase