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

What is the primary mechanism of action for Cyclosporin?

1. Inhibits myeloperoxidase

2. Inhibits calcineurin

3. Stimulates gamma interferon

4. Prevents CD28 activation

The correct answer is: Inhibits calcineurin

Cyclosporin primarily acts by inhibiting calcineurin, which is crucial for T-cell activation. When T cells are activated, they undergo a series of intracellular signaling events that lead to the production of interleukin-2 (IL-2), a key growth factor for T cells. Calcineurin is a calcium-dependent serine/threonine phosphatase that dephosphorylates and activates nuclear factor of activated T cells (NFAT). Once activated, NFAT translocates to the nucleus, promoting IL-2 transcription and T-cell proliferation. By inhibiting calcineurin, cyclosporin effectively prevents the activation of NFAT, subsequently diminishing the production of IL-2 and signaling pathways that lead to T-cell growth and immune response. This mechanism is particularly important in the context of organ transplantation, where suppression of the immune response is necessary to prevent rejection of the transplanted organ. The other options involve different mechanisms not related to cyclosporin's main action. For instance, inhibiting myeloperoxidase pertains to neutrophil function, stimulating gamma interferon is associated with immune response enhancement, and preventing CD28 activation involves a different pathway that regulates T-cell activation. None of these are the primary action