RUTHENIUM RED POTENTLY INHIBITS IMMUNE-RESPONSES BOTH IN-VITRO AND IN-VIVO

Targeted drug screening revealed a compound, Ruthenium Red, which pote ntly blocked proliferation of human T-cells. This compound is not gene rally cytotoxic or cytostatic, as judged by its lack of effect on the proliferation of a panel of transformed cell lines, but it exhibits tr ue immunosuppressive properties. Ruthenium Red inhibits the T-cell pro liferative response (with an Ic(50) similar to 100 nM) to a wide varie ty of agents, including viral antigens from herpes simplex virus, teta nus toroid, alloantigens and IL-2. This compound did not alter the gro wth of an M-CSF-dependent cell line (M-NFS-60) in response to added gr owth factor. Time course studies revealed that Ruthenium Red could be added as late as 24 h after the initiation of T-cell stimulation by an tigen and still produce maximal inhibition, indicating that later stag es of signaling events are being effected. Ruthenium Red was then test ed for its ability to abrogate immune response in vivo. It was discove red that this compound dramatically reduced the expansion of lymphocyt es in draining lymph nodes of mice immunized with cytochrome c in adju vants. Furthermore, Ruthenium Red also suppressed specific antibody pr oduction in mice following challenge with this antigen. The functional properties of Ruthenium Red have been compared with other immunosuppr essive agents and reveal that this compound is most similar to rapamyc in in its overall profile. The chemical structure of Ruthenium Red is quite different from these other agents; therefore, it may be extremel y useful in helping dissect the activation pathway of T-cells. It will be important to explore further the therapeutic potential of this uni que compound.