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Ebselen--an in vivo immune response modifier
A Wendel1, S Kuesters, G Tiegs
1Faculty of Biology, University of Konstanz, Germany.
Biomedical and Environmental Sciences : BES
|October 7, 1997
Summary
Ebselen, a selenoorganic drug, shows promise for autoimmune diseases by modulating cytokine release in mouse models. It reduces harmful inflammatory cytokines and increases beneficial anti-inflammatory ones, protecting against liver injury.
Area of Science:
- Pharmacology
- Immunology
- Hepatology
Background:
- Ebselen (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) possesses known biochemical activities, including GSH peroxidase-like and 5-lipoxygenase inhibitory effects.
- Previous research identified additional activities related to oxidative burst, nitric oxide synthases, protein kinases, and leukocyte migration.
Purpose of the Study:
- To investigate the in vivo immunomodulatory effects of ebselen on cytokine production and action in hyperinflammation models.
- To evaluate ebselen's potential for treating T-cell related autoimmune diseases.
Main Methods:
- Oral administration of ebselen to mice in Concanavalin A-induced and galactosamine-sensitized inflammatory liver injury models.
- Assessment of cytokine levels (Tumor Necrosis Factor alpha, Interferon gamma, Interleukin 10) and liver injury markers.
- Evaluation of ebselen's effect on endotoxin-initiated TNF alpha release and TNF alpha-induced liver injury.
Main Results:
- Ebselen dose-dependently protected mice from T-cell dependent inflammatory liver injury.
- Downregulation of pro-inflammatory cytokines (TNF alpha, IFN gamma) and upregulation of anti-inflammatory cytokine (IL-10) were observed.
- Ebselen inhibited TNF alpha release and attenuated TNF alpha-induced liver injury, while enhancing IL-10 release.
Conclusions:
- Ebselen exhibits significant immunomodulatory properties by altering systemic cytokine profiles in vivo.
- These findings support the development of ebselen for treating T-cell mediated autoimmune diseases.