TY - JOUR
T1 - In vivo effects of mitoxantrone on the production of pro- and anti-inflammatory cytokines by peripheral blood mononuclear cells of secondary progressive multiple sclerosis patients
AU - Angelucci, Francesco
AU - Batocchi, Anna Paola
AU - Caggiula, Marcella
AU - Frisullo, Giovanni
AU - Patanella, Katia
AU - Sancricca, Cristina
AU - Nociti, Viviana
AU - Tonali, Pietro Attilio
AU - Mirabella, Massimiliano
PY - 2006/11
Y1 - 2006/11
N2 - Objective: Mitoxantrone is an antineoplastic agent also used for the treatment of multiple sclerosis (MS). However, despite its efficacy, few data are available on its mechanism of action.The current study was designed to evaluate the short-term (1 month) and long-term (12 months) in vivo effects of mitoxantrone on pro- and anti-inflammatory cytokine production by the peripheral blood mononuclear cells (PBMC) of secondary progressive MS patients. Methods: Eighteen patients with secondary progressive MS underwent mitoxantrone therapy (at a dose of 12 mg/m
2 once every 3 months) over a 1-year period. Blood samples were obtained at baseline, after 1 month and after 12 months of treatment. The production of cytokines in the PBMC was measured by enzyme-linked immunosorbent assay. Results: There were no significant effects of mitoxantrone on proinflammatory cytokines [interleukin (IL) 6 and IL-12p40] and anti-inflammatory cytokines (IL-10 and transforming growth factor-β) in our patients. Patients who showed no signs of therapeutic response were characterized by a higher basal PBMC production of IL-6 compared with that of the responding patients (p <0.05) and mitoxantrone reduced this production after 12 months of treatment (p <0.05). In the responding patients, IL-10 was significantly increased by mitoxantrone after 12 months of treatment (p <0.05). Conclusion: These findings provide additional information useful in the selection of the patient population suitable for mitoxantrone treatment and suggest that most probably the therapeutic action of mitoxantrone in MS is not entirely mediated by its immunosuppressant effects.
AB - Objective: Mitoxantrone is an antineoplastic agent also used for the treatment of multiple sclerosis (MS). However, despite its efficacy, few data are available on its mechanism of action.The current study was designed to evaluate the short-term (1 month) and long-term (12 months) in vivo effects of mitoxantrone on pro- and anti-inflammatory cytokine production by the peripheral blood mononuclear cells (PBMC) of secondary progressive MS patients. Methods: Eighteen patients with secondary progressive MS underwent mitoxantrone therapy (at a dose of 12 mg/m
2 once every 3 months) over a 1-year period. Blood samples were obtained at baseline, after 1 month and after 12 months of treatment. The production of cytokines in the PBMC was measured by enzyme-linked immunosorbent assay. Results: There were no significant effects of mitoxantrone on proinflammatory cytokines [interleukin (IL) 6 and IL-12p40] and anti-inflammatory cytokines (IL-10 and transforming growth factor-β) in our patients. Patients who showed no signs of therapeutic response were characterized by a higher basal PBMC production of IL-6 compared with that of the responding patients (p <0.05) and mitoxantrone reduced this production after 12 months of treatment (p <0.05). In the responding patients, IL-10 was significantly increased by mitoxantrone after 12 months of treatment (p <0.05). Conclusion: These findings provide additional information useful in the selection of the patient population suitable for mitoxantrone treatment and suggest that most probably the therapeutic action of mitoxantrone in MS is not entirely mediated by its immunosuppressant effects.
KW - Cytokines
KW - Interleukin-10
KW - Interleukin-6
KW - Mitoxantrone
KW - Multiple sclerosis
KW - Peripheral blood mononuclear cells
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U2 - 10.1159/000095762
DO - 10.1159/000095762
M3 - Article
C2 - 16974110
AN - SCOPUS:33751351302
VL - 13
SP - 76
EP - 81
JO - NeuroImmunoModulation
JF - NeuroImmunoModulation
SN - 1021-7401
IS - 2
ER -