Inhibition by Mitoxantrone of In Vitro Migration of Immunocompetent Cells

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Abstract
Mitoxantrone hydrochloride is an immunosuppressive drug approved for the treatment of worsening forms of multiple sclerosis (MS).1-3 Like other synthetic anthracenedione, mitoxantrone intercalates with DNA and via interaction with topoisomerase 2 causes DNA single- and double-strand fragmentation.4 As a result, apoptotic and necrotic cell death occurs in treated tissues.5 Studies demonstrated that mitoxantrone affects the innate and adaptive arms of the immune system: the proliferation of macrophages is reduced in vitro and in vivo,6,7 and mitoxantrone interferes with antigen function by inducing programmed cell death of antigen-presenting cells, including dendritic cells8 and macrophages.9 In addition, mitoxantrone reduces the proliferation of T cells and B cells6,7 and decreases the secretion of proinflammatory cytokines.10 However, the precise mechanism of action of mitoxantrone in the treatment of MS remains elusive to date.