| Mechanism of action |
Sirolimus inhibits T lymphocyte activation and proliferation that
occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4,
and IL-15) stimulation by a mechanism that is distinct from that of
other immunosuppressants. Sirolimus also inhibits antibody production.
In cells, sirolimus binds to the immunophilin, FK Binding Protein-12
(FKBP-12), to generate an immunosuppressive complex. The
sirolimus:FKBP-12 complex has no effect on calcineurin activity. This
complex binds to and inhibits the activation of the mammalian Target Of
Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses
cytokine-driven T-cell proliferation, inhibiting the progression from
the G1 to the S phase of the cell cycle. |
