nitrophenols and Lupus-Nephritis

The Bcl-2 family of proteins plays a critical role in controlling immune responses by regulating the expansion and contraction of activated lymphocyte clones by apoptosis. ABT-737, which was originally developed for oncology, is a potent inhibitor of Bcl-2, Bcl-x(L), and Bcl-w protein function. There is evidence that Bcl-2-associated dysregulation of lymphocyte apoptosis may contribute to the pathogenesis of autoimmunity and lead to the development of autoimmune diseases. In this study, we report that ABT-737 treatment resulted in potent inhibition of lymphocyte proliferation as measured by in vitro mitogenic or ex vivo Ag-specific stimulation. More importantly, ABT-737 significantly reduced disease severity in tissue-specific and systemic animal models of autoimmunity. Bcl-2 family antagonism by ABT-737 was efficacious in treating animal models of arthritis and lupus. Our results suggest that treatment with a Bcl-2 family antagonist represents a novel and potentially attractive therapeutic approach for the clinical treatment of autoimmunity.

Topics: Animals; Antigen Presentation; Arthritis, Experimental; Autoimmunity; Biphenyl Compounds; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Disease Progression; Hemocyanins; Humans; Hypersensitivity, Delayed; Interferon-alpha; Lupus Nephritis; Lymphocytes; Mice; Nitrophenols; Piperazines; Proto-Oncogene Proteins c-bcl-2; Substrate Specificity; Sulfonamides