Interferon-beta führt zu einer Stabilisierung der Barriereigenschaften in Hirnkapillarendothelzellen von vier verschiedenen Spezies in vitro

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
J Kraus ◽  
K Voigt ◽  
M Scholz ◽  
A Schuller ◽  
P Oschmann ◽  
...  
Keyword(s):  
Interferon Beta

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

2002 ◽  
Vol 8 (3) ◽  
pp. 237-242 ◽  
Author(s):  
J Hong ◽  
M V Tejada-Simon ◽  
V M Rivera ◽  
Y CQ Zang ◽  
J Z Zhang
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Efficacy ◽  
Interferon Beta ◽  
Viral Infections ◽  
Human Herpesvirus ◽  
Virion Protein ◽  
Cell Free Dna ◽  
Free Dna

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.

scholarly journals Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy P. Sheahan ◽  
Amy C. Sims ◽  
Sarah R. Leist ◽  
Alexandra Schäfer ◽  
John Won ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Interferon Beta ◽  
Lung Pathology ◽  
Kingdom Of Saudi Arabia ◽  
Viral Loads ◽  
Human Infections ◽  
Reduce Virus Replication ◽  
Severe Lung

AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

scholarly journals Interferon-beta enhances sensitivity to gemcitabine in pancreatic cancer

2020 ◽  
Author(s):  
Amber Blaauboer ◽  
Stephanie Booy ◽  
Peter M. van Koetsveld ◽  
Bas Karels ◽  
Fadime Dogan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Colony Formation ◽  
Interferon Beta ◽  
Ex Vivo ◽  
Treatment Resistance ◽  
Proliferating Cells ◽  
Increased Sensitivity

Abstract Background: Adjuvant gemcitabine for pancreatic cancer has limited efficacy in the clinical setting. Impaired drug metabolism is associated with treatment resistance. We aimed to evaluate the chemosensitising effect of interferon-beta (IFN-β).Methods: BxPC-3, CFPAC-1, and Panc-1 cells were pre-treated with IFN-β followed by gemcitabine monotherapy. The effect on cell growth, colony formation, and cell cycle was determined. RT-qPCR was used to measure gene expression. BxPC-3 cells were used in a heterotopic subcutaneous mouse model. Results: IFN-β increased sensitivity to gemcitabine (4-, 7.7-, and 1.7-fold EC50 decrease in BxPC-3, CFPAC-1, and Panc-1, respectively; all P<0.001). Findings were confirmed when assessing colony formation. The percentage of cells in the S-phase was significantly increased after IFN-β treatment only in BxPC-3 and CFPAC-1 by 12% and 7%, respectively (p<0.001 and p<0.05, respectively). Thereby, IFN-β upregulated expression of the drug transporters SLC28A1 in BxPC-3 (252%) and SLC28A3 in BxPC-3 (127%) and CFPAC-1 (223%) (all p<0.001). In vivo, combination therapy reduced tumor volume with 45% (P=0.01). Both ex vivo and in vivo data demonstrate a significant reduction in the number of proliferating cells, whereas apoptosis was increased. Conclusions: For the first time, we validated the chemosensitising effects of IFN-β when combined with gemcitabine in vitro, ex vivo, and in vivo. This was driven by cell cycle modulation and associated with an upregulation of genes involving intracellular uptake of gemcitabine. The use of IFN-β in combination with gemcitabine seems promising in patients with pancreatic cancer and needs to be further explored.

scholarly journals Interferon-beta enhances sensitivity to gemcitabine in pancreatic cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Amber Blaauboer ◽  
Stephanie Booy ◽  
Peter M. van Koetsveld ◽  
Bas Karels ◽  
Fadime Dogan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Colony Formation ◽  
Interferon Beta ◽  
Ex Vivo ◽  
Treatment Resistance ◽  
Proliferating Cells ◽  
Increased Sensitivity

Abstract Background Adjuvant gemcitabine for pancreatic cancer has limited efficacy in the clinical setting. Impaired drug metabolism is associated with treatment resistance. We aimed to evaluate the chemosensitising effect of interferon-beta (IFN-β). Methods BxPC-3, CFPAC-1, and Panc-1 cells were pre-treated with IFN-β followed by gemcitabine monotherapy. The effect on cell growth, colony formation, and cell cycle was determined. RT-qPCR was used to measure gene expression. BxPC-3 cells were used in a heterotopic subcutaneous mouse model. Results IFN-β increased sensitivity to gemcitabine (4-, 7.7-, and 1.7-fold EC50 decrease in BxPC-3, CFPAC-1, and Panc-1, respectively; all P < 0.001). Findings were confirmed when assessing colony formation. The percentage of cells in the S-phase was significantly increased after IFN-β treatment only in BxPC-3 and CFPAC-1 by 12 and 7%, respectively (p < 0.001 and p < 0.05, respectively). Thereby, IFN-β upregulated expression of the drug transporters SLC28A1 in BxPC-3 (252%) and SLC28A3 in BxPC-3 (127%) and CFPAC-1 (223%) (all p < 0.001). In vivo, combination therapy reduced tumor volume with 45% (P = 0.01). Both ex vivo and in vivo data demonstrate a significant reduction in the number of proliferating cells, whereas apoptosis was increased. Conclusions For the first time, we validated the chemosensitising effects of IFN-β when combined with gemcitabine in vitro, ex vivo, and in vivo. This was driven by cell cycle modulation and associated with an upregulation of genes involving intracellular uptake of gemcitabine. The use of IFN-β in combination with gemcitabine seems promising in patients with pancreatic cancer and needs to be further explored.

Effects of Interferon Beta, Cyclophosphamide and Azathioprine on Cytokine Profile in Patients with Multiple Sclerosis

2005 ◽  
Vol 18 (2) ◽  
pp. 377-383 ◽  
Author(s):  
R. Totaro ◽  
A. Passacantando ◽  
T. Russo ◽  
I. Parzanese ◽  
M. Rascente ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Th2 Cytokines ◽  
Positive Interaction ◽  
Tnf Α ◽  
Ifn Γ

We assessed the in vitro effects of interferon beta-1b (IFNβ-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNβ-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNβ-1b, CY, and AZA alone or with the combination of IFNβ-1b with CY or AZA. The combination of IFNβ-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alfa (TNF-α) (P=0.03). An additive effect on the production of interferon gamma (IFN-γ) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNβ-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-α (P=0.02), IFN-γ (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNβ-1b on the ratio of Th1/Th2 cytokines.

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