Introduction. Multiple Sclerosis (MS) patients run an increased risk of microbial infections. Although immunotherapy may increase infection risk in some cases, data as to the relationship among microbial factors, disease-modifying treatments (DMTs) and alterations in the innate immunity of these patients are still scanty. Our previous study indicated that MS polymorphonuclear cells (PMNs) have a significant reduction in intracellular killing activity compared to healthy subject (HS) PMNs, related to the therapeutic management of patients. On this ground, the aim of this study was to evaluate the direct role of most common immunosuppressive or immunomodulatory MS therapeutic agents on the functions of HS neutrophils subjected to an in vitro drug pretreatment. Materials and Methods. To achieve this purpose HS PMNs were pre-treated with natalizumab (NAT), fingolimod (FTY), interferon β 1b (INFβ) or glatiramer acetate (GA), and then their intracellular killing activity towards Klebsiella pneumoniae, cytokine release profile, apoptosis, reactive oxygen species (ROS) production and surface molecule expression were investigated. Results. In vitro assays with drug pre-treated HS PMNs showed a reduction in bacterial killing with significantly lower values (p<0.001) than those registered for the un-pre-treated controls for all the DMTs assayed. In the same experimental conditions variable results, depending on the DMT used, for the other examined neutrophil functions were achieved. In fact, this defective neutrophil killing was also associated with a significantly lower ROS production, a slight increase of survival and cytokine production for FTY, and a lower cytokine release pattern for both INFβ and GA. Conclusions. In this regard, a deeper understanding of the priming condition exerted by treatments in neutrophils from MS patients could be a clue for the complete comprehension of MS pathogenesis and may be later utilized for therapeutic purposes that may prevent neutrophil-mediated damage to host tissues. In the end, the validation of these results could help in identifying a subset of patients at high risk of infection who could benefit from a closer follow-up and/or antibiotic prophylaxis.
NEW INSIGHTS INTO THE ROLE OF MULTIPLE SCLEROSIS TREATMENT ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS AGAINST PATHOGENS
ALLIZOND, Valeria;SCUTERA, SARA AGATA CATERINA;Piersigilli, Giorgia;MUSSO, Tiziana;CAVALLA, PAOLA;TREBINI, CLAUDIA;MARRA, ELISA SIMONA;TULLIO, Viviana Cristina;MANDRAS, Narcisa;ROANA, Janira;CUFFINI, Annamaria;BANCHE, Giuliana
2016-01-01
Abstract
Introduction. Multiple Sclerosis (MS) patients run an increased risk of microbial infections. Although immunotherapy may increase infection risk in some cases, data as to the relationship among microbial factors, disease-modifying treatments (DMTs) and alterations in the innate immunity of these patients are still scanty. Our previous study indicated that MS polymorphonuclear cells (PMNs) have a significant reduction in intracellular killing activity compared to healthy subject (HS) PMNs, related to the therapeutic management of patients. On this ground, the aim of this study was to evaluate the direct role of most common immunosuppressive or immunomodulatory MS therapeutic agents on the functions of HS neutrophils subjected to an in vitro drug pretreatment. Materials and Methods. To achieve this purpose HS PMNs were pre-treated with natalizumab (NAT), fingolimod (FTY), interferon β 1b (INFβ) or glatiramer acetate (GA), and then their intracellular killing activity towards Klebsiella pneumoniae, cytokine release profile, apoptosis, reactive oxygen species (ROS) production and surface molecule expression were investigated. Results. In vitro assays with drug pre-treated HS PMNs showed a reduction in bacterial killing with significantly lower values (p<0.001) than those registered for the un-pre-treated controls for all the DMTs assayed. In the same experimental conditions variable results, depending on the DMT used, for the other examined neutrophil functions were achieved. In fact, this defective neutrophil killing was also associated with a significantly lower ROS production, a slight increase of survival and cytokine production for FTY, and a lower cytokine release pattern for both INFβ and GA. Conclusions. In this regard, a deeper understanding of the priming condition exerted by treatments in neutrophils from MS patients could be a clue for the complete comprehension of MS pathogenesis and may be later utilized for therapeutic purposes that may prevent neutrophil-mediated damage to host tissues. In the end, the validation of these results could help in identifying a subset of patients at high risk of infection who could benefit from a closer follow-up and/or antibiotic prophylaxis.
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