A Long-Acting Tumor Necrosis Factor a-Binding Protein Demonstrates Activity in Both In Vitro and In Vivo Models of Endometriosis.

Altan, Z.M., Denis, D., Kagan, D., Grund, E.M., Palmer, S.S., Nataraja, S.G.
Journal   J Pharmacol.
Species  
Analytes Measured   GM-CSF , IL-6 , IL-8 , MCP-1
Matrix Tested   Cell culture supernatants
Year   2010
Volume   334
Page Numbers   460-466
Application   Cytokines and Chemokines
Abstract
Endometriosis is characterized by the presence of elevated proinflammatory cytokines such as tumor necrosis factor (TNF) alpha in the peritoneal cavity. Blocking interaction of TNFalpha with its receptor by the addition of excess TNFalpha-binding protein (TBP)-1 (a soluble form of TNF receptor-1) was effective in animal models of endometriosis. Recently, a novel, high-affinity inhibitor of TNFalpha, TNF-soluble high-affinity receptor complex (TNF-SHARC), was created by fusing TBP to both the alpha and beta subunits of inactive human chorionic gonadotropin. This dimeric protein was effective in inhibiting collagen-induced arthritis in mice. In the present study, the efficacy of TNF-SHARC in cellular and in vivo models of endometriosis was examined. TBP and TNF-SHARC dose-dependently inhibited TNFalpha-induced secretion of interleukin (IL)-6, IL-8, granulocyte macrophage-colony-stimulating factor, and monocyte chemoattractant protein-1 in immortalized human endometriotic cells. An in vivo mouse model of experimentally induced endometriosis using cycling C57BL/6 mice was established. Antide treatment (0.5 mg/kg), used as positive control, initiated 7 days after the establishment of the disease, reduced the weight of the lesions compared with control. TNF-SHARC at 3 mg/kg was not effective in inhibiting the disease, whereas at 9 mg/kg there was reduction in the lesion weight. In addition, antide and TNF-SHARC treatment in vivo increased in vitro natural killer cell activity compared with untreated animals. Thus, we provide evidence for supporting the development of TNF-SHARC as a therapeutic candidate for treating endometriosis in human.

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Multiplex
V-PLEX Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 2 Human Kit
IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α | Human
Multiplex
V-PLEX Viral Panel 1 NHP Kit
IL-1β, IL-6, IL-8 | Non-human primate
Multiplex
V-PLEX Viral Panel 1 Human Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 2 Human Kit
IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit
IL-1β, IL-6, IL-8 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 1 Human Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
U-PLEX Human GM-CSF Assay
GM-CSF | Human
Singleplex
U-PLEX Human MCP-1 Assay
MCP-1 | Human
Singleplex
U-PLEX Human IL-8 Assay
IL-8 | Human
Singleplex
U-PLEX Human IL-6 Assay
IL-6 | Human
Singleplex
U-PLEX Mouse GM-CSF Assay
GM-CSF | Mouse
Singleplex
U-PLEX NHP GM-CSF Assay
GM-CSF | Non-human primate
Singleplex
U-PLEX Mouse IL-6 Assay
IL-6 | Mouse
Singleplex
U-PLEX NHP MCP-1 Assay
MCP-1 | Non-human primate
Singleplex
U-PLEX NHP IL-8 Assay
IL-8 | Non-human primate
Singleplex
U-PLEX NHP IL-6 Assay
IL-6 | Non-human primate
Singleplex
U-PLEX Mouse MCP-1 Assay
MCP-1 | Mouse
Singleplex
R-PLEX Rat MCP-1 Assay
MCP-1 | Rat
Singleplex
R-PLEX Rat IL-6 Assay
IL-6 | Rat
Singleplex
R-PLEX Rat GM-CSF Assay
GM-CSF | Rat
Singleplex
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