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.
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).


CONCLUSIONS
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.
Angelucci
Francesco
F
Department of Neuroscience, Institute of Neurology, Catholic University, Rome, Italy.
Batocchi
Anna Paola
AP
Caggiula
Marcella
M
Frisullo
Giovanni
G
Patanella
Katia
K
Sancricca
Cristina
C
Nociti
Viviana
V
Tonali
Pietro Attilio
PA
Mirabella
Massimiliano
M
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D013995:Time; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D008942:Mitoxantrone