201. 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.
- Author
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Angelucci F, Batocchi AP, Caggiula M, Frisullo G, Patanella K, Sancricca C, Nociti V, Tonali PA, and Mirabella M
- Subjects
- Adult, Antineoplastic Agents pharmacology, Cells, Cultured, Cytokines blood, Cytokines immunology, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunosuppressive Agents pharmacology, Inflammation Mediators blood, Inflammation Mediators immunology, Interleukin-10 blood, Interleukin-10 immunology, Interleukin-12 Subunit p40 blood, Interleukin-12 Subunit p40 immunology, Interleukin-6 blood, Interleukin-6 immunology, Leukocytes, Mononuclear metabolism, Male, Middle Aged, Multiple Sclerosis, Chronic Progressive blood, Time, Transforming Growth Factor beta blood, Transforming Growth Factor beta immunology, Treatment Outcome, Up-Regulation drug effects, Up-Regulation immunology, Cytokines drug effects, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear immunology, Mitoxantrone pharmacology, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive immunology
- Abstract
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-beta) 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.
- Published
- 2006
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