Ebselen--an in vivo immune response modifier.
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Ebselen--an in vivo immune response modifier. / Wendel, A; Kuesters, S; Tiegs, Gisa.
In: BIOMED ENVIRON SCI, Vol. 10, No. 2-3, 2-3, 1997, p. 253-259.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Ebselen--an in vivo immune response modifier.
AU - Wendel, A
AU - Kuesters, S
AU - Tiegs, Gisa
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Liver Failure/prevention & control
KW - Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use
KW - Azoles/pharmacology/therapeutic use
KW - Lymphocyte Activation/drug effects
KW - Organoselenium Compounds/pharmacology/therapeutic use
KW - Superantigens/pharmacology
KW - T-Lymphocytes/drug effects/immunology
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Liver Failure/prevention & control
KW - Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use
KW - Azoles/pharmacology/therapeutic use
KW - Lymphocyte Activation/drug effects
KW - Organoselenium Compounds/pharmacology/therapeutic use
KW - Superantigens/pharmacology
KW - T-Lymphocytes/drug effects/immunology
M3 - SCORING: Journal article
VL - 10
SP - 253
EP - 259
JO - BIOMED ENVIRON SCI
JF - BIOMED ENVIRON SCI
SN - 0895-3988
IS - 2-3
M1 - 2-3
ER -