Inhibition of Human Neutrophil Functions In Vitro by Multiple Sclerosis Disease-Modifying Therapies
Open Access
- 2 November 2020
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (11), 3542
- https://doi.org/10.3390/jcm9113542
Abstract
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 Klebsiella pneumoniae, whereas none of them affected the rate of neutrophil apoptosis or CD11b and CD62L cell surface expression. Intriguingly, only FTY exposure negatively affected K. pneumoniae-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.Keywords
This publication has 57 references indexed in Scilit:
- Neutrophil cell surface receptors and their intracellular signal transduction pathwaysInternational Immunopharmacology, 2013
- Glatiramer Acetate Increases Phagocytic Activity of Human Monocytes In Vitro and in Multiple Sclerosis PatientsPLOS ONE, 2012
- Sphingosine-1-phosphate signaling and its role in diseaseTrends in Cell Biology, 2012
- Synergistic effect of erythromycin on polymorphonuclear cell antibacterial activity against erythromycin-resistant phenotypes of Streptococcus pyogenesInternational Journal of Antimicrobial Agents, 2010
- Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluidMultiple Sclerosis Journal, 2009
- Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1β in human monocytes and multiple sclerosisProceedings of the National Academy of Sciences of the United States of America, 2009
- In vitro evaluation of the effect of a novel immunosuppressive agent, FTY720, on the function of feline neutrophilsAmerican Journal of Veterinary Research, 2006
- Increased CXCL8 (IL-8) expression in Multiple SclerosisJournal of Neuroimmunology, 2004
- In VivoEffects of Recombinant-Interferon-β1bTreatment on Polymorphonuclear Cell and Monocyte Functions and On T-Cell-Mediated Antibacterial Activity in Patients with Relapsing-Remitting Multiple SclerosisImmunopharmacology and Immunotoxicology, 2000
- Different patterns of cytokine regulation of phagocytosis and bacterial killing by human neutrophilsInternational Journal of Antimicrobial Agents, 1996