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Published on: March 26, 2019
Effects of pixantrone on immune-cell function in the course of acute rat experimental allergic encephalomyelitis
Benedetta Mazzanti1, Tiziana Biagioli, Alessandra Aldinucci
1Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy.
Abstract:
Pixantrone is an immunesuppressor similar to mitoxantrone but with lower cardiotoxicity. We evaluated the effect of pixantrone on B cells and lymphomononuclear cells in the course of acute EAE. Pixantrone reduced the number of B cells and suppressed myelin basic protein (MBP) specific IgG production. In vitro, pixantrone induced apoptosis of rat B lymphocytes in a way similar to mitoxantrone. In addition, pixantrone inhibited antigen specific and mitogen induced lymphomononuclear cell proliferation, as well as IFN-gamma production, during EAE. These findings suggest a similar mechanism of action for pixantrone and mitoxantrone on the effector function of lymphomonocyte B and T cells.
Insights
Pixantrone, an immunesuppressor, reduces B cells and inhibits T cell proliferation and IFN-gamma production in experimental autoimmune encephalomyelitis (EAE). It demonstrates a similar mechanism of action to mitoxantrone with potentially lower cardiotoxicity.
Area of Science:
- Immunology
- Pharmacology
- Neuroscience
Background:
- Pixantrone is an immunesuppressor drug with structural similarities to mitoxantrone.
- Mitoxantrone is associated with significant cardiotoxicity, a concern for long-term use.
- The therapeutic potential of pixantrone, particularly its immunomodulatory effects and safety profile, warrants investigation.
Purpose of the Study:
- To evaluate the effects of pixantrone on B cells and lymphomononuclear cells in the context of acute experimental autoimmune encephalomyelitis (EAE).
- To compare the in vitro mechanisms of action of pixantrone and mitoxantrone on immune cells.
Main Methods:
- Administration of pixantrone during the course of acute EAE in a rat model.
- Assessment of B cell counts and myelin basic protein (MBP) specific IgG production.
- In vitro studies to evaluate the effect of pixantrone on rat B lymphocyte apoptosis.
- Measurement of lymphomononuclear cell proliferation and interferon-gamma (IFN-gamma) production in response to antigens and mitogens.
Main Results:
- Pixantrone treatment led to a reduction in B cell numbers within the EAE model.
- The drug suppressed the production of MBP-specific IgG antibodies.
- In vitro, pixantrone induced apoptosis in rat B lymphocytes, similar to mitoxantrone.
- Pixantrone inhibited both antigen-specific and mitogen-induced lymphomononuclear cell proliferation.
- IFN-gamma production by these cells during EAE was also inhibited by pixantrone.
Conclusions:
- Pixantrone exhibits significant immunomodulatory effects, impacting both B and T cell functions in EAE.
- The findings suggest that pixantrone shares a similar mechanism of action with mitoxantrone regarding the effector functions of lymphomonocyte B and T cells.
- Pixantrone's potential for reduced cardiotoxicity compared to mitoxantrone makes it a promising candidate for further investigation in autoimmune and inflammatory conditions.
