Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens
Open Access
- 1 March 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Journal of Inflammation Research
- Vol. ume 13, 151-164
- https://doi.org/10.2147/jir.s243514
Abstract
Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the re-myelination.Keywords
This publication has 38 references indexed in Scilit:
- On The Role of Natural Killer Cells in Neurodegenerative DiseasesToxins, 2013
- Survival in MSNeurology, 2012
- Glatiramer Acetate in the Treatment of Multiple SclerosisCNS Drugs, 2011
- Rituximab Therapy Reduces Organ-Specific T Cell Responses and Ameliorates Experimental Autoimmune EncephalomyelitisPLOS ONE, 2011
- AltAnalyze and DomainGraph: analyzing and visualizing exon expression dataNucleic Acids Research, 2010
- The Double-Edged Sword of Autoimmunity: Lessons from Multiple SclerosisToxins, 2010
- Depletion of functionally active CD20+ T cells by rituximab treatmentArthritis & Rheumatism, 2009
- Autoimmune T cell responses in the central nervous systemNature Reviews Immunology, 2009
- Lymphoid neogenesis in chronic inflammatory diseasesNature Reviews Immunology, 2006
- Defining the clinical course of multiple sclerosisNeurology, 1996