AIDS is a severe, transmissible form of immune deficiency caused by infection with HIV. Several neoplasms are seen in greatly elevated frequency in AIDS and HIV infection. AIDS-KS is the most common AIDS- related malignancy. In autopsy surveys, it is seen in up to 60% of patients with HIV infection. Previous studies showed that IL-6 was important in the proliferation of AIDS-KS cells in vitro. For example, both IL-6 and the IL-6 receptor are found in cultured AIDS-Kaposi's sarcoma derived cells and in KS lesions in vivo. Direct modulation of the IL-6 pathway has been used to therapeutic advantage in trials of trans-retinoic acid, intra-lesion monoclonal antibodies to IL-6, and interleukin-4 in patients with KS. Another cytokine, tumor necrosis factor has been shown to increase the growth of AIDS-KS cells in culture through an IL-6 dependent pathway. Since TNF is elevated in patients with HIV infection, this maybe a mechanism of increased KS tumor growth. In this proposal, we will evaluate a new therapeutic agent for KS, soluble TNF receptors. It is believed that this agent will decrease circulating TNF activity resulting in a regression of tumors. A core laboratory for the processing and analysis of cytokine and receptor expression in KS tissue will be used. These will studies will support the clinical trials effort and will verify the proposed mechanisms of action. It is hoped that this well directed and targeted effort will improve survival for patients with AIDS related Kaposi's sarcoma.
| Panyutich, E A; Said, J W; Miles, S A (1998) Infection of primary dermal microvascular endothelial cells by Kaposi's sarcoma-associated herpesvirus. AIDS 12:467-72 |
