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Polymorphonuclear Cell Functional Impairment in Relapsing Remitting Multiple Sclerosis Patients: Preliminary Data.

Allizond V, Scutera S, Rossi S, Musso T, Crocillà C, Cavalla P, Trebini C, Marra ES, Cuffini AM, Banche G - PLoS ONE (2015)

Bottom Line: The in vitro ability of PMNs from patients, either untreated or treated with immunosuppressant or immunomodulatory drugs to kill Klebsiella pneumonia or Candida albicans, were investigated and compared to PMNs from healthy subjects.Our results indicate that although patients have a normal number of PMNs, they have a statistically significant (p<0.05) reduction in intracellular killing activity.As no statistically significant differences were observed between patients and controls in cytokine release values, reactive oxygen species production or apoptosis, we came to the conclusion that other factors may be involved.

View Article: PubMed Central - PubMed

Affiliation: Bacteriology and Mycology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy.

ABSTRACT
Multiple Sclerosis patients run an increased risk of microbial infections, which leads to high rates of hospitalization and infection-related mortality. Although immunotherapy may increase infection risk in some cases, data as to the relationship among microbial factors, immunotherapy and alterations in the innate immunity of these patients are still scanty. On these grounds, this interdisciplinary study aims at investigating the role the functional activity of polymorphonuclear cells (PMNs) play in relapsing remitting multiple sclerosis at different stages. The in vitro ability of PMNs from patients, either untreated or treated with immunosuppressant or immunomodulatory drugs to kill Klebsiella pneumonia or Candida albicans, were investigated and compared to PMNs from healthy subjects. The release of various cytokines was also assessed, as was the production of reactive oxygen species and their ability to regulate apoptosis after microbial stimulation. Our results indicate that although patients have a normal number of PMNs, they have a statistically significant (p<0.05) reduction in intracellular killing activity. Although variations are strongly related to the therapeutic management of patients, they are independent from their disease stage. As no statistically significant differences were observed between patients and controls in cytokine release values, reactive oxygen species production or apoptosis, we came to the conclusion that other factors may be involved. Supportive validation of these results from further studies might well help in identifying a subset of patients at high risk of infection who could benefit from a closer follow-up and/or antibiotic prophylaxis.

No MeSH data available.


Related in: MedlinePlus

The analysis of induced oxidative burst in MS patients.Whole blood from healthy subjects (HS; n = 12), from untreated-MS patients (n = 7), from patients treated with immunosuppressive drugs (IS-MS; n = 6) or with immunomodulatory drugs (IM-MS; n = 12), was stimulated with K. pneumoniae (A), C. albicans (B) or PMA (C) for 30 minutes. Percentage of positive cells for DHR123 (left panels) or average of fluorescence intensity (MFI) of DHR123 (right panels) were determined by flow cytometry. Data are represented as average ± SEM.
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pone.0131557.g002: The analysis of induced oxidative burst in MS patients.Whole blood from healthy subjects (HS; n = 12), from untreated-MS patients (n = 7), from patients treated with immunosuppressive drugs (IS-MS; n = 6) or with immunomodulatory drugs (IM-MS; n = 12), was stimulated with K. pneumoniae (A), C. albicans (B) or PMA (C) for 30 minutes. Percentage of positive cells for DHR123 (left panels) or average of fluorescence intensity (MFI) of DHR123 (right panels) were determined by flow cytometry. Data are represented as average ± SEM.

Mentions: The neutrophil intracellular ROS production from untreated or treated RR-MS patients and HSs was examined and compared, to assess whether the generation of ROS is involved in the various intracellular killing activities in MS patients. Superoxide production was measured by flow cytometry in whole blood neutrophils stimulated by K. pneumoniae, C. albicans, PMA, or left untreated. The percentage of PMNs that produce ROS in response to the different stimuli was very similar between the groups, irrespective of treatment (Fig 2, left panels); these results were also confirmed by the MFI expression (Fig 2, right panels).


Polymorphonuclear Cell Functional Impairment in Relapsing Remitting Multiple Sclerosis Patients: Preliminary Data.

Allizond V, Scutera S, Rossi S, Musso T, Crocillà C, Cavalla P, Trebini C, Marra ES, Cuffini AM, Banche G - PLoS ONE (2015)

The analysis of induced oxidative burst in MS patients.Whole blood from healthy subjects (HS; n = 12), from untreated-MS patients (n = 7), from patients treated with immunosuppressive drugs (IS-MS; n = 6) or with immunomodulatory drugs (IM-MS; n = 12), was stimulated with K. pneumoniae (A), C. albicans (B) or PMA (C) for 30 minutes. Percentage of positive cells for DHR123 (left panels) or average of fluorescence intensity (MFI) of DHR123 (right panels) were determined by flow cytometry. Data are represented as average ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488035&req=5

pone.0131557.g002: The analysis of induced oxidative burst in MS patients.Whole blood from healthy subjects (HS; n = 12), from untreated-MS patients (n = 7), from patients treated with immunosuppressive drugs (IS-MS; n = 6) or with immunomodulatory drugs (IM-MS; n = 12), was stimulated with K. pneumoniae (A), C. albicans (B) or PMA (C) for 30 minutes. Percentage of positive cells for DHR123 (left panels) or average of fluorescence intensity (MFI) of DHR123 (right panels) were determined by flow cytometry. Data are represented as average ± SEM.
Mentions: The neutrophil intracellular ROS production from untreated or treated RR-MS patients and HSs was examined and compared, to assess whether the generation of ROS is involved in the various intracellular killing activities in MS patients. Superoxide production was measured by flow cytometry in whole blood neutrophils stimulated by K. pneumoniae, C. albicans, PMA, or left untreated. The percentage of PMNs that produce ROS in response to the different stimuli was very similar between the groups, irrespective of treatment (Fig 2, left panels); these results were also confirmed by the MFI expression (Fig 2, right panels).

Bottom Line: The in vitro ability of PMNs from patients, either untreated or treated with immunosuppressant or immunomodulatory drugs to kill Klebsiella pneumonia or Candida albicans, were investigated and compared to PMNs from healthy subjects.Our results indicate that although patients have a normal number of PMNs, they have a statistically significant (p<0.05) reduction in intracellular killing activity.As no statistically significant differences were observed between patients and controls in cytokine release values, reactive oxygen species production or apoptosis, we came to the conclusion that other factors may be involved.

View Article: PubMed Central - PubMed

Affiliation: Bacteriology and Mycology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy.

ABSTRACT
Multiple Sclerosis patients run an increased risk of microbial infections, which leads to high rates of hospitalization and infection-related mortality. Although immunotherapy may increase infection risk in some cases, data as to the relationship among microbial factors, immunotherapy and alterations in the innate immunity of these patients are still scanty. On these grounds, this interdisciplinary study aims at investigating the role the functional activity of polymorphonuclear cells (PMNs) play in relapsing remitting multiple sclerosis at different stages. The in vitro ability of PMNs from patients, either untreated or treated with immunosuppressant or immunomodulatory drugs to kill Klebsiella pneumonia or Candida albicans, were investigated and compared to PMNs from healthy subjects. The release of various cytokines was also assessed, as was the production of reactive oxygen species and their ability to regulate apoptosis after microbial stimulation. Our results indicate that although patients have a normal number of PMNs, they have a statistically significant (p<0.05) reduction in intracellular killing activity. Although variations are strongly related to the therapeutic management of patients, they are independent from their disease stage. As no statistically significant differences were observed between patients and controls in cytokine release values, reactive oxygen species production or apoptosis, we came to the conclusion that other factors may be involved. Supportive validation of these results from further studies might well help in identifying a subset of patients at high risk of infection who could benefit from a closer follow-up and/or antibiotic prophylaxis.

No MeSH data available.


Related in: MedlinePlus