Effects of mitoxantrone on multiple sclerosis patients' lymphocyte subpopulations and production of immunoglobulin, TNF-alpha and IL-10.
We designed this longitudinal study to clarify the short- and long-term effects of mitoxantrone on the immune system in a subgroup of multiple sclerosis patients treated at our centre. After 14 days we found a highly significant sustained reduction of leucocytes, primarily affecting neutrophils and most lymphocyte subsets except for naive and activated T lymphocytes. The CD4/CD8 ratio and serum immmunoglobulin levels were not affected. Furthermore, whole blood-stimulated mononuclear cell IL-10 production showed a significant lower level 2 weeks treatment, whereas basal IL-10 as well as stimulated and basal TNF-alpha secretion showed no significant changes. Longitudinal data disclosed a persistent decrease of B lymphocytes, while secretion of immunoglobulins, IL-10, and TNF-alpha was not altered in the follow-up. In conclusion, we confirmed a selective short-term effect of mitoxantrone therapy on most lymphocyte subpopulations, but not on immunoglobulines or the pro- and anti-inflammatory cytokines TNF-alpha and IL-10, which do not serve as possible response markers.
Gbadamosi
Joystone
J
Department of Neurology, University Hospital Hamburg, Germany. gbadamosi@uke.uni-hamburg.de
Buhmann
Carsten
C
Tessmer
Wiebke
W
Moench
Andrea
A
Haag
Friedrich
F
Heesen
Christoph
C
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D007958:Leukocyte Count; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008942:Mitoxantrone