Mitoxantrone treatment in multiple sclerosis induces TH2-type cytokines.
OBJECTIVE
Mitoxantrone is a cytotoxic drug with immune modulatory properties used in the treatment of progressive forms of multiple sclerosis (MS). We explored the effect of mitoxantrone treatment in MS patients on cytokine patterns induced in peripheral blood mononuclear cells (PBMC) and T-cell subsets ex vivo.


METHODS
Blood was obtained before mitoxantrone infusion and 6, 12 and 18 days thereafter. Proliferation and prototypic TH1-, TH17- and TH2-type cytokines were determined following in vitro stimulation of PBMC, CD4+ and CD8+ T cells. In addition, a patient cohort receiving its first mitoxantrone treatment was cross-sectionally compared with a cohort of patients with more than 1 year of treatment.


RESULTS
Mitoxantrone treatment increased the ex vivo production of the TH2 cytokines interleukin-4 (IL-4; P < 0.05) and IL-5 (P < 0.001) in phytohemagglutinin-stimulated CD4+ T cells within 18 days of treatment. The cross-sectional study revealed that long-term treatment with mitoxantrone increased the inducibility of IL-4 and IL-5 secretion by PBMCs and CD4+ T cells even further. No significant changes were observed for interferon-γ, tumour necrosis factor-α, IL-17 and IL-10. Mitoxantrone did not alter the proliferative capacity of ex vivo-stimulated T cells.


CONCLUSIONS
Mitoxantrone treatment in MS enhances the inducibility of TH2-type cytokines, which may contribute to its beneficial effects in MS.
Vogelgesang
A
A
Department of Neurology, University of Greifswald, Greifswald, Germany.
Rosenberg
S
S
Skrzipek
S
S
Bröker
B M
BM
Dressel
A
A
D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
D016207:Cytokines; D008942:Mitoxantrone