title: Treatment with natalizumab in relapsing-remitting multiple sclerosis patients induces changes in inflammatory mechanism.
abstract: 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 pro-inflammatory 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-1β 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.
authors.affiliation: Neuroscience Research Laboratory, Health Research Institute (IdiPAZ), University Hospital La Paz/Autónoma University of Madrid, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ramos-Cejudo
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Luiz
authors.initials: L
authors.lastname: Stark Aroeira
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez de Antonio
authors.forename: Beatriz
authors.initials: B
authors.lastname: Chamorro
authors.forename: Exuperio
authors.initials: E
authors.lastname: Diez-Tejedor
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000069442:Natalizumab; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D039041:Integrin alpha4beta1; D000069442:Natalizumab