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Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function
Journal of Immunology (Baltimore, Md. : 1950)
|July 15, 1986
Summary
Mitoxantrone, an anti-cancer drug, suppresses the humoral immune system. It reduces B cell numbers and inhibits their proliferation, impacting antibody production.
Area of Science:
- Immunology
- Pharmacology
Background:
- Mitoxantrone is an antineoplastic agent with antiproliferative effects.
- Its potential immunomodulating properties are under investigation.
Purpose of the Study:
- To investigate the impact of mitoxantrone on B lymphocyte reactivity.
- To elucidate the mechanisms underlying mitoxantrone's immunomodulatory effects.
Main Methods:
- Mice were treated with mitoxantrone (0.5 mg/kg daily for 14 days).
- Humoral immune responses were assessed via in vivo and in vitro antibody production assays (ovalbumin, SRC, TNP-LPS, TNP-Ficoll).
- B cell function was evaluated using T cell-replacing factor reconstitution, LPS-induced mitogenesis assays, and flow cytometry.
Main Results:
- Mitoxantrone abrogated both thymus-dependent and thymus-independent antibody responses.
- B cells were identified as a direct target of mitoxantrone's suppressive activity.
- Mitoxantrone inhibited LPS-induced B cell proliferation, an effect partially restored by depleting adherent cells.
- Flow cytometry showed a significant decrease in splenic B lymphocyte count.
Conclusions:
- Mitoxantrone potently suppresses the humoral immune system.
- This suppression is mediated by a reduction in B cell numbers and macrophage-mediated inhibition of B cell proliferation.