Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies
There is a growing optimism about the potential of new disease-modifying therapies (DMTs) in the management of relapsing-remitting multiple sclerosis (RRMS) patients. However, this initial enthusiasm has been tempered by evidence indicating that multiple sclerosis (MS) patients undergoing DMT may be...
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doaj-9f3c6beb33994f5a97ebf1227675092a2020-11-25T03:41:02ZengMDPI AGJournal of Clinical Medicine2077-03832020-11-0193542354210.3390/jcm9113542Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying TherapiesSara Scutera0Tiziana Musso1Paola Cavalla2Giorgia Piersigilli3Rosaria Sparti4Sara Comini5Marco Vercellino6Anna Maria Cuffini7Giuliana Banche8Valeria Allizond9Department of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Neuroscience, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Neuroscience, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyDepartment of Public Health and Pediatrics, University of Torino, 10126 Turin, ItalyThere is a growing optimism about the potential of new disease-modifying therapies (DMTs) in the management of relapsing-remitting multiple sclerosis (RRMS) patients. However, this initial enthusiasm has been tempered by evidence indicating that multiple sclerosis (MS) patients undergoing DMT may be at higher risk of developing infections through incompletely understood mechanisms. As neutrophils provide the first line of defense against pathogens, here we have compared the effects of some of the commonly used MS DMTs (i.e., moderate-efficacy injective, first-line: interferonβ-1b (IFNβ-1b), glatiramer acetate (GA); and high-efficacy, second-line: fingolimod (FTY) and natalizumab (NAT)) on the in vitro viability and functions of neutrophils isolated from healthy subjects. All the DMTs tested impaired the ability of neutrophils to kill <i>Klebsiella</i><i> pneumoniae</i>, whereas none of them affected the rate of neutrophil apoptosis or CD11b and CD62L cell surface expression. Intriguingly, only FTY exposure negatively affected <i>K. pneumoniae</i>-induced production of reactive oxygen species (ROS) in polymorphonuclear leukocytes (PMNs). Furthermore, neutrophils exposed to K. pneumoniae secreted enhanced amounts of CXCL8, IL-1β and TNF-α, which were differentially regulated following DMT pretreatment. Altogether, these findings suggest that DMTs may increase the susceptibility of MS patients to microbial infections, in part, through inhibition of neutrophil functions. In light of these data, we recommend that the design of personalized therapies for RRMS patients should take into account not just the mechanism of action of the chosen DMT but also the potential risk of infection associated with the administration of such therapeutic compounds to this highly vulnerable population.https://www.mdpi.com/2077-0383/9/11/3542disease-modifying therapiesmultiple sclerosisneutrophil functions<i>Klebsiella pneumoniae</i> |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sara Scutera Tiziana Musso Paola Cavalla Giorgia Piersigilli Rosaria Sparti Sara Comini Marco Vercellino Anna Maria Cuffini Giuliana Banche Valeria Allizond |
spellingShingle |
Sara Scutera Tiziana Musso Paola Cavalla Giorgia Piersigilli Rosaria Sparti Sara Comini Marco Vercellino Anna Maria Cuffini Giuliana Banche Valeria Allizond Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies Journal of Clinical Medicine disease-modifying therapies multiple sclerosis neutrophil functions <i>Klebsiella pneumoniae</i> |
author_facet |
Sara Scutera Tiziana Musso Paola Cavalla Giorgia Piersigilli Rosaria Sparti Sara Comini Marco Vercellino Anna Maria Cuffini Giuliana Banche Valeria Allizond |
author_sort |
Sara Scutera |
title |
Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies |
title_short |
Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies |
title_full |
Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies |
title_fullStr |
Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies |
title_full_unstemmed |
Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies |
title_sort |
inhibition of human neutrophil functions in vitro by multiple sclerosis disease-modifying therapies |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-11-01 |
description |
There is a growing optimism about the potential of new disease-modifying therapies (DMTs) in the management of relapsing-remitting multiple sclerosis (RRMS) patients. However, this initial enthusiasm has been tempered by evidence indicating that multiple sclerosis (MS) patients undergoing DMT may be at higher risk of developing infections through incompletely understood mechanisms. As neutrophils provide the first line of defense against pathogens, here we have compared the effects of some of the commonly used MS DMTs (i.e., moderate-efficacy injective, first-line: interferonβ-1b (IFNβ-1b), glatiramer acetate (GA); and high-efficacy, second-line: fingolimod (FTY) and natalizumab (NAT)) on the in vitro viability and functions of neutrophils isolated from healthy subjects. All the DMTs tested impaired the ability of neutrophils to kill <i>Klebsiella</i><i> pneumoniae</i>, whereas none of them affected the rate of neutrophil apoptosis or CD11b and CD62L cell surface expression. Intriguingly, only FTY exposure negatively affected <i>K. pneumoniae</i>-induced production of reactive oxygen species (ROS) in polymorphonuclear leukocytes (PMNs). Furthermore, neutrophils exposed to K. pneumoniae secreted enhanced amounts of CXCL8, IL-1β and TNF-α, which were differentially regulated following DMT pretreatment. Altogether, these findings suggest that DMTs may increase the susceptibility of MS patients to microbial infections, in part, through inhibition of neutrophil functions. In light of these data, we recommend that the design of personalized therapies for RRMS patients should take into account not just the mechanism of action of the chosen DMT but also the potential risk of infection associated with the administration of such therapeutic compounds to this highly vulnerable population. |
topic |
disease-modifying therapies multiple sclerosis neutrophil functions <i>Klebsiella pneumoniae</i> |
url |
https://www.mdpi.com/2077-0383/9/11/3542 |
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