AUTHOR=Sehr Tony , Akgün Katja , Haase Rocco , Ziemssen Tjalf 

TITLE=Fingolimod Leads to Immediate Immunological Changes Within 6 h After First Administration

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00391

DOI=10.3389/fneur.2020.00391

ISSN=1664-2295

ABSTRACT=<p><bold>Objective:</bold> Multiple effects of fingolimod have already been described. Here we investigated the acute effects on immune cell subsets and identified correlations with autonomic first dose phenomena and long-term immunological effects.</p><p><bold>Methods:</bold> Blood samples of 20 MS patients were analyzed using FACS. Immune cell frequencies before and at defined prospective time points beginning 6 h after first fingolimod administration were evaluated in parallel to cardiovascular autonomic and clinical parameters.</p><p><bold>Results:</bold> A significant decrease of absolute lymphocyte count (1.81GPt/l to 1.42GPt/l), CD3+ (1.34GPt/l to 1.06GPt/l), CD3+CD4+ (0.94GPt/l to 0.73GPt/l), and CD19+ (0.26GPt/l to 0.19GPt/l) cells could be already demonstrated within 6 hours after first dose which correspond to a relative reduction by 28, 23, 23% resp. 29% in relation to the longterm steady state cell frequency level. Short- and long-term effects were significantly correlated for lymphocytes, CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD14+, and NK cells as well as for neutrophil granulocytes. In addition, correlations could be found between reduced heart rate (68.95–60.05 bpm) and the decrease in CD3+, CD3+CD4+, and CD19+ cells after 6 h.</p><p><bold>Conclusions:</bold> Early immunological changes could already be detected 6 h after fingolimod first dose. Most of the acute changes correlate with long-term modulation. A link between the acute immunological and cardiological effects was found.</p>