Anti-viral properties of interferon beta treatment in patients with multiple sclerosis

Viral infections are potentially associated with the etiology and pathogenesis of multiple sclerosis (MS). It has been speculated that the treatment efficacy of interferon beta (IFN beta) in MS may relate to its anti-viral properties. The study was undertaken to evaluate the in vivo anti-viral effects of IFN beta-1a in patients with MS. Human herpesvirus-6 (HHV-6) was studied as an example for being a latent neurotropic virus. IFN beta used at concentrations of approximately 0.5 mg/ml was shown to significantly reduce in vitro HHV-6 replication in a susceptible T-cell line. Sera derived from 23 MS patients treated with IFN beta-1a were examined for serum cell-free DNA of HHV-6 as an indicator for viral replication and the reactivity of IgM antibodies to a recombinant HHV-6 virion protein containing a known immunoreactive region. The results were compared with those of control sera obtained from untreated MS (n=29) and healthy individuals (n=21). The findings indicated that IFN beta treatment significantly reduced HHV-6 replication as evident by decreased cell-free DNA in treated MS specimens. The results correlated with decreased IgM reactivity to the HHV-6 antigen in treated MS patients compared to untreated controls, suggesting reduced exposure to HHV-6. The findings were confirmed in paired sera obtained from seven MS patients before and after the treatment. The study provides new evidence indicating that IFN beta has potent in vivo anti-viral effects that may contribute to the treatment efficacy in MS.

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Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival

Journal of Clinical Medicine ◽

10.3390/jcm9051543 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1543 ◽

Cited By ~ 2

Author(s):

Felix Krenzien ◽

Shadi Katou ◽

Alba Papa ◽

Bruno Sinn ◽

Christian Benzing ◽

...

Keyword(s):

Liver Transplantation ◽

Immune Responses ◽

Viral Infections ◽

Inflammatory Responses ◽

Term Survival ◽

Cell Free Dna ◽

Reactive Protein ◽

Free Dna

Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits highly proinflammatory effects via DNA sensors. Herein, we measured cfDNA after liver transplantation and found elevated levels when organs from resuscitated donors were transplanted. High levels of cfDNA were associated with high C-reactive protein, leukocytosis as well as granulocytosis in the recipient. In addition to increased systemic immune responses, portal hepatitis was observed, which was associated with increased interface activity and a higher numbers of infiltrating neutrophils and eosinophils in the graft. In fact, the cfDNA was an independent significant factor in multivariate analysis and increased concentration of cfDNA was associated with inferior 1-year survival. Moreover, cfDNA levels were found to be decreased significantly during the postoperative course when patients underwent continuous veno-venous haemofiltration. In conclusion, patients receiving livers from resuscitated donors were characterised by high postoperative cfDNA levels. Those patients showed pronounced portal hepatitis and systemic inflammatory responses in the short term leading to a high mortality. Further studies are needed to evaluate the clinical relevance of cfDNA clearance by haemoadsorption and haemofiltration in vitro and in vivo.

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T cell-T cell activation in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/135245859700300404 ◽

1997 ◽

Vol 3 (4) ◽

pp. 238-242 ◽

Cited By ~ 7

Author(s):

JW Lindsey ◽

RH Kerman ◽

JS Wolinsky

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Viral Infections ◽

Activated T Cells ◽

In Vitro Proliferation

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

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Interferon beta treatment of multiple sclerosis increases serum interleukin-7

Multiple Sclerosis Journal ◽

10.1177/1352458514532700 ◽

2014 ◽

Vol 20 (13) ◽

pp. 1727-1736 ◽

Cited By ~ 4

Author(s):

Wangko Lundström ◽

Christina Hermanrud ◽

Maria Sjöstrand ◽

Susanna Brauner ◽

Marie Wahren-Herlenius ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Interferon Beta ◽

Blood Leukocytes ◽

Interleukin 7 ◽

Cell Counts ◽

Cell Immunity ◽

Polymerase Chain

Background: Interleukin-7 (IL-7) is a non-redundant cytokine for T-cell development and survival. The IL-7 signaling pathway has been genetically and functionally associated with several autoimmune diseases including multiple sclerosis (MS). Objective: The objective of this paper is to elucidate the effect of the widely used immunomodulatory MS therapy interferon beta (IFNβ) on IL-7 homeostasis. Methods: Swedish MS patients were screened for IL-7 concentration in serum and blood cell counts. IL-7 receptor alpha chain (IL-7Rα) expression was determined by semi-quantitative real-time polymerase chain reaction (PCR) and flow cytometry. Results: IFNβ treatment led to significantly increased serum IL-7 levels (mean: 17 pg/ml) compared with healthy controls (mean: 7.6 pg/ml) and natalizumab-treated patients (mean: 5.3 pg/ml). In vitro and in vivo, peripheral blood leukocytes showed decreased IL-7Rα expression and IL-7 consumption upon IFNβ exposure, suggesting that their IL-7 responsiveness is impaired during treatment. Conclusions: MS patients undergoing IFNβ treatment have increased serum IL-7 levels and decreased IL-7 consumption. Given IL-7’s important role in T-cell immunity, this relationship may be highly relevant for IFNβ’s treatment efficacy.

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Sustained in vitro interferon-beta release and in vivo toxicity of PLGA and PEG-PLGA nanoparticles

RSC Advances ◽

10.1039/c9ra09928j ◽

2020 ◽

Vol 10 (27) ◽

pp. 15893-15900 ◽

Cited By ~ 3

Author(s):

Andrea Fodor-Kardos ◽

Ádám Ferenc Kiss ◽

Katalin Monostory ◽

Tivadar Feczkó

Keyword(s):

Multiple Sclerosis ◽

Interferon Beta ◽

Plga Nanoparticles ◽

In Vivo Toxicity ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

Interferon-beta-1a (IFN-β-1a) can diminish the symptoms of relapsing-remitting multiple sclerosis.

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Seminal cell-free DNA levels measured by PicoGreen fluorochrome are associated with sperm fertility criteria

Zygote ◽

10.1017/s0967199416000307 ◽

2017 ◽

Vol 25 (2) ◽

pp. 111-119 ◽

Cited By ~ 13

Author(s):

F. Costa ◽

F. Barbisan ◽

C.E. Assmann ◽

N.K.F. Araújo ◽

A.R. de Oliveira ◽

...

Keyword(s):

Superoxide Anion ◽

Sperm Viability ◽

Cell Free Dna ◽

Free Dna ◽

Cell Mortality ◽

Potential Association ◽

Dye Staining ◽

Male Patients

SummaryPrevious investigations suggested that elevated cell-free DNA (cfDNA) can indicate non-healthy states. However, the potential association between cfDNA seminal plasma levels and fertility sperm parameters has not yet been determined. Therefore, the present study evaluated the association between seminal cfDNA levels and sperm fertility criteria to determine the use of seminal cfDNA quantification. An in vivo protocol quantified cfDNA levels of semen samples obtained from 163 male patients using fluorescent PicoGreen dye staining. To confirm if semen cfDNA quantification is realistic, an in vitro complementary test was performed using three or four semen samples. The fresh sperm samples were exposed to paraquat that generates high levels of superoxide anion causing oxidative stress and cell mortality. The results showed significant association between dsDNA levels and several sperm fertility parameters, such as low viability and alterations of motility and morphology. The in vitro analysis confirmed the association between dsDNA levels and sperm viability. Together, these results suggest that dsDNA levels could be an important biomarker to test sperm fertility.

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