A growing body of evidence indicates that the central nervous system (CNS) and immune system are two super-systems closely linked and that this functional interaction could pave the way to appearance of immunological manifestations as the result of CNS injury, and vice versa. Multiple sclerosis (MS) is considered a T-cell-mediated autoimmune disease of the CNS. Literature data report that MS patients are at a noticeably infection raised risk leading to hospital admission and infection-related mortality, and also immunotherapy may influence this increasing risk. Data on the relationship among microbial factors, immunotherapies and alterations of the innate immunity in MS patients are still lacking. This study investigated the role of innate immune system in MS patients either treated or untreated with immunosuppressant/immunomodulatory drugs, at different stages of development and with different clinical classification, in comparison with healthy subjects (HSs). We compared the in vitro functional activity (phagocyte microbicidal activity and cytokine release profile) of granulocytes (PMNs) harvested from 15 MS patients with that of 9 HS-PMNs against Klebsiella pneumoniae. The microbicidal activity towards intracellular bacteria by MS-PMNs was significantly depressed within 60’ of incubation: intracellular Survival Index (SI) was >2 for treated patients, indicating total absence of killing and active intracellular multiplication of klebsiellae and 1.96 (4% of killing) for untreated patients. On the contrary, HS-PMNs in the same experimental conditions were effectively able to kill ingested bacteria (IS= 1.48; 52% of killing at 30’ and IS=1.74; 26% of killing at 60’). The proinflammatory cytokine release in the supernatants of PMNs after 30’ of incubation with bacteria revealed a gradual increased level of all cytokines during the incubation time, but no statistically significant differences were observed in these values between MS patients and HSs. These findings provide evidence that even though in MS patients the number of PMNs is normal, their primary functions are altered, independently to MS status but in a way related to the treatment. This altered PMN function seems not dependent on the cytokine release pattern and could be due to a decreased activity of the respiratory burst. The validation of these results could help in identifying a subset of patients at high infection risk who could benefit from a closer follow-up or antibiotic prophylaxis.
PHAGOCYTES IN MULTIPLE SCLEROSIS: ALTERED MICROBICIDAL FUNCTIONS RELATED TO THE DISEASE
ALLIZOND, VALERIA;SCUTERA, SARA AGATA CATERINA;MUSSO, Tiziana;MANDRAS, Narcisa;TULLIO, Viviana Cristina;MARRA, ELISA SIMONA;CUFFINI, Annamaria;BANCHE, Giuliana
2013-01-01
Abstract
A growing body of evidence indicates that the central nervous system (CNS) and immune system are two super-systems closely linked and that this functional interaction could pave the way to appearance of immunological manifestations as the result of CNS injury, and vice versa. Multiple sclerosis (MS) is considered a T-cell-mediated autoimmune disease of the CNS. Literature data report that MS patients are at a noticeably infection raised risk leading to hospital admission and infection-related mortality, and also immunotherapy may influence this increasing risk. Data on the relationship among microbial factors, immunotherapies and alterations of the innate immunity in MS patients are still lacking. This study investigated the role of innate immune system in MS patients either treated or untreated with immunosuppressant/immunomodulatory drugs, at different stages of development and with different clinical classification, in comparison with healthy subjects (HSs). We compared the in vitro functional activity (phagocyte microbicidal activity and cytokine release profile) of granulocytes (PMNs) harvested from 15 MS patients with that of 9 HS-PMNs against Klebsiella pneumoniae. The microbicidal activity towards intracellular bacteria by MS-PMNs was significantly depressed within 60’ of incubation: intracellular Survival Index (SI) was >2 for treated patients, indicating total absence of killing and active intracellular multiplication of klebsiellae and 1.96 (4% of killing) for untreated patients. On the contrary, HS-PMNs in the same experimental conditions were effectively able to kill ingested bacteria (IS= 1.48; 52% of killing at 30’ and IS=1.74; 26% of killing at 60’). The proinflammatory cytokine release in the supernatants of PMNs after 30’ of incubation with bacteria revealed a gradual increased level of all cytokines during the incubation time, but no statistically significant differences were observed in these values between MS patients and HSs. These findings provide evidence that even though in MS patients the number of PMNs is normal, their primary functions are altered, independently to MS status but in a way related to the treatment. This altered PMN function seems not dependent on the cytokine release pattern and could be due to a decreased activity of the respiratory burst. The validation of these results could help in identifying a subset of patients at high infection risk who could benefit from a closer follow-up or antibiotic prophylaxis.
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