Current state of the art in the field of organ transplantation employs various immunosuppressive agents to prevent post-surgical allograft rejection by the host. However, these pharmacological agents often result in many adverse side effects due to the quantities of medication that are required following transplantation. Cyclosporins, tacrilomus, mycophenclate mofetil and rapamycin are among the drugs commonly used today.
The efficacy of these drugs can be attributed to their ability to act as immunosuppressive agents, whereby inhibiting the lymphocyte activation pathway. In turn, the transplanted tissue is not subject to the deleterious effects of the host immune response.
Cytotoxic agents may also be utilized in immunosuppression. Upon antigenic activation, lymphocytes rapidly proliferate as part of the immune response. Cytotoxic agents kill rapidly dividing cells, such as lymphocytes and therefore inhibit activation.
Utilizing both these immunosuppressive mechanisms, UCLA scientists have determined that perillyl alcohol, a widely-known anti-carcinogen, can be used to reduce graft rejection. By inhibiting activation of the p2l ras oncogene, perillyl alcohol blocks activation of the pathway necessary for lymphocyte proliferation and thus activation. In addition, perillyl alcohol can also reduce the side effects of current anti-rejection agents. By working in a pathway different from its counterparts, perillyl alcohol can be administered alone or in conjunction with other immunosuppressive drugs. Therefore, the doses of these established drugs are decreased and the overall side effects are reduced.
These findings suggest that perillyl alcohol may be an important mediator in the field of transplantation surgery by preventing acute and chronic graft rejection. Furthermore, its well-documented anti-carcinogenic and anti-microbial properties may prove to be highly beneficial to immunocompromised transplant patients.
|United States Of America||Issued Patent||6,133,324||10/17/2000||1999-229|