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Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens
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, w...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082624/ https://www.ncbi.nlm.nih.gov/pubmed/32214838 http://dx.doi.org/10.2147/JIR.S243514 |
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author | Al-ani, Mena R Raju, Tom K Hachim, Mahmood Y Hachim, Ibrahim Y Elemam, Noha M Guimei, Maha Bendardaf, Riyad Maghazachi, Azzam A |
author_facet | Al-ani, Mena R Raju, Tom K Hachim, Mahmood Y Hachim, Ibrahim Y Elemam, Noha M Guimei, Maha Bendardaf, Riyad Maghazachi, Azzam A |
author_sort | Al-ani, Mena R |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7082624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-70826242020-03-25 Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens Al-ani, Mena R Raju, Tom K Hachim, Mahmood Y Hachim, Ibrahim Y Elemam, Noha M Guimei, Maha Bendardaf, Riyad Maghazachi, Azzam A J Inflamm Res Original Research 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. Dove 2020-03-10 /pmc/articles/PMC7082624/ /pubmed/32214838 http://dx.doi.org/10.2147/JIR.S243514 Text en © 2020 Al-ani et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Al-ani, Mena R Raju, Tom K Hachim, Mahmood Y Hachim, Ibrahim Y Elemam, Noha M Guimei, Maha Bendardaf, Riyad Maghazachi, Azzam A Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title | Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title_full | Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title_fullStr | Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title_full_unstemmed | Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title_short | Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens |
title_sort | rituximab prevents the development of experimental autoimmune encephalomyelitis (eae): comparison with prophylactic, therapeutic or combinational regimens |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082624/ https://www.ncbi.nlm.nih.gov/pubmed/32214838 http://dx.doi.org/10.2147/JIR.S243514 |
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