Question

Which of the following statements best describes the mechanism of action of cyclosporine? It a. binds to and inhibits m-TOR b. increases apoptosis of T lymphocytes c. binds to cyclophilin and inhibits calcineurin d. binds to steroid nuclear receptors e. inhibits tyrosine kinase phosphorylation of certain $G$ protein coupled receptors

Short answer

Answer: Cyclosporine binds to cyclophilin and inhibits calcineurin, which in turn prevents the activation of T-Lymphocytes, by blocking the transcription of genes encoding for cytokines like IL-2.

Step-by-step solution

Understand the question

In this question, we have to find the correct statement describing the mechanism of action of cyclosporine, an immunosuppressive drug used for organ transplant patients.

Analyze the options

We need to go through each option and analyze them to understand if they describe the mechanism of action of cyclosporine: a. binds to and inhibits m-TOR b. increases apoptosis of T lymphocytes c. binds to cyclophilin and inhibits calcineurin d. binds to steroid nuclear receptors e. inhibits tyrosine kinase phosphorylation of certain $G$ protein-coupled receptors.

Eliminate incorrect options

We can eliminate some options as they do not describe the mechanism of action of cyclosporine: a. binds to and inhibits m-TOR: This is the mechanism of action for drugs like sirolimus and not cyclosporine. b. increases apoptosis of T lymphocytes: Cyclosporine does not work by increasing apoptosis; rather, it prevents the activation of T-Lymphocytes. d. binds to steroid nuclear receptors: This is the mechanism of action for corticosteroids, not cyclosporine. e. inhibits tyrosine kinase phosphorylation of certain $G$ protein-coupled receptors: This is not the mechanism of action for cyclosporine, but for certain kinase inhibitors.

Identify the correct option

After eliminating the other options, we are left with only one choice: c. binds to cyclophilin and inhibits calcineurin

Conclusion

The correct statement that best describes the mechanism of action of cyclosporine is: Cyclosporine binds to cyclophilin and inhibits calcineurin, which in turn prevents the activation of T-Lymphocytes, by blocking the transcription of genes encoding for cytokines like IL-2.

Key concepts

Immunosuppressive Drugs

Immunosuppressive drugs are a critical component of modern medicine, particularly in the context of organ transplantation and autoimmune diseases. Their main role is to dampen or suppress the immune system's response, which can be essential for preventing the rejection of transplanted organs or for managing inflammatory and autoimmune conditions.

Examples of immunosuppressive drugs include glucocorticoids, calcineurin inhibitors, m-TOR inhibitors, and more specialized agents like monoclonal antibodies and small molecules targeting various aspects of the immune signaling pathways. Each drug has a unique mechanism of action and cyclosporine, discussed in this exercise, is a cornerstone in the family of calcineurin inhibitors.

It is crucial to note, however, that while these drugs help in controlling immune responses, they also increase the risk of infections and cancer due to the suppressed immune system's reduced ability to protect the body effectively.

T-Lymphocyte Inhibition

T-lymphocytes, known commonly as T-cells, are a type of white blood cell vital for the body’s immune response. They are primarily responsible for identifying and mounting a defense against pathogens, and for perpetuating autoimmune responses. In the context of immunosuppression, specifically after organ transplantation, it’s essential to inhibit T-cell activation to prevent the body from attacking the transplanted tissue as foreign material.

To achieve this, drugs like cyclosporine strategically prevent the activation of T-cells by inhibiting certain pathways necessary for their function. Without this activation, the T-cells are unable to proliferate and carry out their role in the immune response, thus reducing the likelihood of organ rejection. The role cyclosporine plays in this process is crucial, and its specific action provides the basis for its effectiveness as an immunosuppressive agent.

Calcineurin Inhibition

Calcineurin is a protein phosphatase, an enzyme that is crucial for activating T-lymphocytes. It does so by dephosphorylating another protein called NFAT (nuclear factor of activated T-cells), which then travels into the nucleus and initiates the transcription of genes that produce cytokines necessary for the immune response, such as interleukin-2 (IL-2).

Cyclosporine inhibits calcineurin by forming a complex with cyclophilin, another cellular protein. The cyclosporine-cyclophilin complex then binds to calcineurin and blocks its activity. This inhibition prevents the dephosphorylation of NFAT and, as a result, NFAT cannot enter the nucleus to trigger cytokine production. Thus, the activation of T-lymphocytes is suppressed, reducing the immune response and helping prevent organ transplant rejection. This distinctive action characterizes cyclosporine's mechanism and establishes its value as an immunosuppressive medication.