Ds. Dwyer et al., RUTHENIUM RED POTENTLY INHIBITS IMMUNE-RESPONSES BOTH IN-VITRO AND IN-VIVO, International journal of immunopharmacology, 17(11), 1995, pp. 931-940
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.