American Board of Surgery Qualifying Exam (ABS QE) Practice Test

What is the primary mechanism of action of FK506 (Tacrolimus)?

1. Binds FK and inhibits calcineurin

2. Inhibits IL-2 production

3. Depletes CD4+ lymphocytes

4. Modulates histamine release

The correct answer is: Binds FK and inhibits calcineurin

The primary mechanism of action of FK506, commonly known as Tacrolimus, involves its ability to bind to a cytosolic protein called FKBP (FK506-binding protein). When Tacrolimus binds to FKBP, this complex then inhibits calcineurin, a calcium-dependent phosphatase that plays a crucial role in T-cell activation. Calcineurin is responsible for dephosphorylating the nuclear factor of activated T-cells (NFAT), which allows NFAT to translocate into the nucleus and promote the transcription of interleukin-2 (IL-2) and other cytokines that are essential for T-cell proliferation and activation. By inhibiting calcineurin, Tacrolimus effectively reduces the production of IL-2, thereby dampening the immune response. Understanding this mechanism is central to recognizing why Tacrolimus is utilized, especially in the context of transplant immunosuppression. Its ability to selectively inhibit T-cell activation makes it a potent drug in preventing organ rejection. The other choices present various immunological effects or pathways that are influenced by different drugs or mechanisms but do not accurately capture the primary action of Tacrolimus. For example, while it indirectly reduces IL-2 production as a consequence of calcine