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

Endometriosis is characterized by the presence of elevated proinflammatory cytokines such as tumor necrosis factor (TNF) in the peritoneal cavity. Blocking interaction of TNF with its receptor by the addition of excess TNF-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 TNF, TNF-soluble high-affinity receptor complex (TNF-SHARC), was created by fusing TBP to both the and 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 TNF-induced secretion of interleukin (IL)-6, IL-8, granulocyte macrophage–colony-