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Pitt transplant researchers say anti-rejection drug rapamycin may help lupus, some cancers

PITTSBURGH, Jan. 22 Rapamycin, a drug approved for use in kidney transplant patients to prevent organ rejection, could also benefit patients with lupus and other autoimmune diseases as well as patients with blood cancers, such as acute myeloid leukemia, reports a team of researchers from the University of Pittsburgh's Thomas E. Starzl Transplantation Institute and Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig University in Giessen, Germany.

Their conclusions, outlined in a paper to be published in the journal Blood and currently posted on the journal's Web site (www.bloodjournal.org), were based on two key discoveries about rapamycin's mechanisms.

First, while rapamycin suppresses immune system T cells, as many anti-rejection drugs do, the researchers found that the drug also inhibits the function and activation of dendritic cells, cells that play a much earlier role in the immune response as the first cells to identify foreign intruders. They in turn present these intruders to other immune system cells, including T cells.

Second, and perhaps more surprising to the study's authors, rapamycin disarms the trigger that allows dendritic cells to proliferate. This trigger, a potent, naturally occurring growth factor, also affects the proliferation of blood precursor and stem cells, which if allowed to grow unchecked, result in leukemia and other cancers.

"Rapamycin's effect on dendritic cells impairs immune reactivity at the earliest stages. Because dendritic cells are important for the initiation and regulation of immune response, this effect is very important. Our findings provide novel insight into the pharmacology of this agent and have significant implications for the development of new therapeutic strategies in disease processes in which dendritic cells play a crucial immunopathological role," stated Angus W. Thomson, Ph.D., D.Sc., professor of surgery and immu
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Contact: Lisa Rossi
412-647-3555
University of Pittsburgh Medical Center
22-Jan-2003


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