ABSTRACT
Rapamycin (sirolimus; Rapamune®) is a macrocyclic lactone produced by Streptomyces hygroscopicus. It inhibits T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine stimulation, particularly interleukine (IL)-2, IL-4, and IL-5 by a mechanism that differs from other immunosuppressants. Rapamycin binds FK binding protein-12 (FKBP12) and the complex inhibits the activation of a key regulatory kinase, the mammalian Target Of Rapamycin (mTOR). This inhibition in turn suppresses cytokine-driven T-cell proliferation and its progression from the G1 to the S phase of the cell cycle. This profound inhibition of proliferation, migration, and inflammation make this agent useful in treating acute renal allograft rejection and allograft arteriopathy (Table 4.1).13 Animal studies have shown that the systemic administration of rapamycin is highly effective in decreasing intimal proliferation and restenosis after balloon angioplasty.14
