In Vitro and In Vivo Immunosuppressive Activity of a Novel Anthracycline, 13-deoxy, 5-iminodoxorubicin 1
| Autor: | Olson, Richard D., Headley, Mark B., Hodzic, Alma, Walsh, Gerald M., Wingett, Denise G. |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Mice Inbred BALB C Tumor Necrosis Factor-alpha CD40 Ligand Anti-Inflammatory Agents Interleukin-2 Receptor alpha Subunit Dermatitis Contact Article Leukocyte Count Mice Doxorubicin Echocardiography Animals Humans Interleukin-2 Dinitrofluorobenzene Heart Atria Rabbits Cells Cultured Immunosuppressive Agents Cell Proliferation |
| Popis: | We report that the novel anthracycline analog, 13-deoxy, 5-iminodoxorubicin (DIDOX), represents a potentially new class of immunosuppressive agents. DIDOX has been structurally modified from the parent compound, doxorubicin, to remove the carbonyl group at carbon-13 and the quinone moiety at carbon-5 since these structures likely mediate the cardiotoxic side effects of this family of chemotherapeutic drugs. Our studies demonstrate that DIDOX inhibits T cell proliferation and the expression of the T cell activation molecules, CD25 and CD40L. DIDOX also inhibits the production of the pro-inflammatory cytokine, TNF-alpha and IL-2. Studies using animal models demonstrate that DIDOX inhibits the inflammation accompanying contact hypersensitivity reactions and possesses reduced cardiotoxicity compared to doxorubicin. These findings indicate that DIDOX has important immunosuppressive activities that may warrant the development of this new and improved anthracycline for the treatment of T cell-mediated inflammatory diseases. |
| Databáze: | OpenAIRE |
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