Ebselen--an in vivo immune response modifier

Numerous biochemical activities are known for the selenoorganic drug ebselen [(2-phenyl-1,2-benzoisoselenazol-3-(2H)-one]. The initial interest focussed on its GSH peroxidase-like activity and its inhibitory activity on 5-lipoxygenase, however, further activities of the drug on oxidative burst of leukocytes, nitric oxide synthases, protein kinases and on leukocyte migration were recognized. Here we report that Ebselen differentially interacts in vivo with the production and action of systemically released cytokines in various hyperinflammation models in mice. Ebselen given orally to mice protected dose-dependently from Concanavalin A-induced, T-cell dependent inflammatory liver injury. The release of the proinflammatory cytokines Tumor Necosis Factor alpha and Interferon gamma was downregulated, while the production of the anti-inflammatory cytokine Interleukin 10 was increased. Similar results were found in galactosamine-sensitized mice in an inflammatory liver model using the superantigen staphylococcal enterotoxin B as a T-cell activator. Moreover, Ebselen inhibited the release of TNF alpha initiated by endotoxin in vivo in mice. In galactosamine-pretreated mice. Ebselen also attenuated liver injury induced by recombinant Tumor Necosis Factor alpha and initiated enhanced release of Interleukin 10. These findings expand the pharmacological knowledge on ebselen to hitherto unknown immunomodulatory properties which encourage to develop the drug for treatment of T-cell related autoimmune diseases.