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Treatment with natalizumab in relapsing-remitting multiple sclerosis patients induces changes in inflammatory mechanism

Journal of Clinical Immunology, ISSN: 0271-9142, Vol: 31, Issue: 4, Page: 623-631
2011
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Article Description

Natalizumab is a widely accepted drug for the relapsing-remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of proinflammatory interferon gamma and interleukin (IL)- 12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL- 13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1ß increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation. © Springer Science+Business Media, LLC 2011.

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