What is ciclosporin?: An Immunosuppressant Explained

October 7, 2025 •

4 min read

First isolated from a soil fungus in 1971, ciclosporin was the first highly effective immunosuppressive drug to be discovered. This medication works by dampening the immune system's response to prevent the body from rejecting transplanted organs and to manage various autoimmune conditions.

Quick Summary

Ciclosporin is a potent immunosuppressant medication that prevents the body's immune system from rejecting transplanted organs and treats autoimmune conditions like rheumatoid arthritis and psoriasis.

Key Points

Immunosuppressive Action: Ciclosporin suppresses the immune system by inhibiting T-lymphocytes, the key cells involved in immune rejection and autoimmune attacks.
Mechanism: It works by binding to cyclophilin, which then blocks the calcineurin enzyme, preventing the activation of T-cells and the production of pro-inflammatory cytokines like IL-2.
Primary Uses: Its main applications include preventing organ transplant rejection and treating severe autoimmune disorders such as rheumatoid arthritis, psoriasis, and atopic dermatitis.
Common Side Effects: Common adverse effects include hypertension, kidney damage, increased hair growth, and gum overgrowth.
Monitoring is Key: Due to potential toxicity and numerous drug interactions, careful monitoring of blood levels and kidney function is required.
Forms and Absorption: Modified formulations (like Neoral®) offer more consistent and predictable absorption than older, unmodified versions (Sandimmune®).

The Core Function of Ciclosporin

Ciclosporin (also known as cyclosporine in the US) is a powerful immunosuppressant agent belonging to the class of medications called calcineurin inhibitors. It works by significantly decreasing the activity of the body's immune system, primarily targeting and suppressing T-lymphocytes (T-cells). This ability to selectively inhibit T-cell function makes it an indispensable tool in modern medicine for preventing organ rejection and managing a variety of autoimmune diseases. While highly effective, it requires careful dosage management and monitoring due to its narrow therapeutic window and potential for side effects.

How Ciclosporin Inhibits the Immune Response

The pharmacological effect of ciclosporin is centered on its ability to inhibit calcineurin, an enzyme crucial for T-cell activation. The process involves several key steps:

Binding to Cyclophilin: Upon entering a T-cell, ciclosporin binds to a cytosolic protein called cyclophilin, forming a complex.
Inhibiting Calcineurin: This ciclosporin-cyclophilin complex then binds to and inhibits calcineurin's phosphatase activity.
Blocking Gene Transcription: Normally, calcineurin activates a transcription factor called NFAT (Nuclear Factor of Activated T-cells). By blocking calcineurin, ciclosporin prevents the dephosphorylation and subsequent translocation of NFAT to the cell nucleus.
Preventing Cytokine Production: Without activated NFAT, the transcription of critical cytokine genes, such as interleukin-2 (IL-2), is inhibited. IL-2 is essential for the activation and proliferation of T-cells, so its suppression effectively halts the immune attack.

Key Medical Applications of Ciclosporin

Ciclosporin's immunosuppressive properties make it essential for treating several medical conditions, including:

Organ Transplantation: The most common application is to prevent the rejection of a transplanted organ, such as a kidney, liver, or heart. It is typically used in combination with other medications.
Rheumatoid Arthritis: For severe, active cases in adults who have not responded well to other treatments like methotrexate.
Psoriasis: Used to treat severe, recalcitrant plaque psoriasis that is not responsive to other systemic therapies.
Atopic Dermatitis: Used for the short-term treatment of severe cases in adults.
Nephrotic Syndrome: Manages certain kidney disorders, such as focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).
Dry Eyes (Keratoconjunctivitis Sicca): An ophthalmic emulsion of ciclosporin is used to increase tear production caused by ocular inflammation.

Potential Side Effects and Drug Interactions

Like many potent medications, ciclosporin carries a risk of side effects, which necessitate careful monitoring by a healthcare provider.

Common side effects include:

Increased hair growth (hirsutism)
Swollen gums (gingival hyperplasia)
High blood pressure (hypertension)
Headache
Kidney problems
Stomach upset, such as nausea, diarrhea, and heartburn
Tremors or shaking
Increased risk of infection, especially fungal and viral infections

More serious side effects can include:

Liver dysfunction
Increased risk of certain cancers, particularly skin cancer and lymphoma, with long-term use
Neurotoxicity, with symptoms like seizures, confusion, and changes in vision

Due to its metabolism via the CYP3A4 enzyme system in the liver, ciclosporin has numerous drug interactions. Important considerations include:

Avoid Grapefruit: Grapefruit and grapefruit juice can significantly increase ciclosporin levels in the blood, leading to a higher risk of toxicity.
Other Medications: A thorough review of all prescribed and over-the-counter medications is necessary, as many, including certain antibiotics, antifungals, and herbal products like St. John's wort, can alter ciclosporin levels.
Therapeutic Drug Monitoring: Given the narrow therapeutic index, blood levels are regularly monitored to ensure effectiveness while minimizing the risk of toxicity.

Ciclosporin vs. Tacrolimus: A Comparison of Calcineurin Inhibitors

Ciclosporin is often compared to tacrolimus, another calcineurin inhibitor used for similar indications. While they share a common mechanism, they exhibit different potency levels and side effect profiles.


Feature	Ciclosporin	Tacrolimus
Potency	Less potent than tacrolimus, requiring higher doses.	Up to 100 times more potent than ciclosporin.
Formulation	Older, original formulation (Sandimmune®) has erratic absorption; newer microemulsion formulations (Neoral®, Gengraf®) offer better absorption.	Oral formulations have relatively low bioavailability but consistent absorption.
Common Side Effects	Hirsutism, gingival hyperplasia, high blood pressure, and kidney damage are common.	Neurotoxicity (headache, tremor), gastrointestinal issues (diarrhea, nausea), and new-onset diabetes are more frequent.
Post-Transplant Diabetes	Lower incidence compared to tacrolimus.	Higher incidence compared to ciclosporin.
Effect on Rejection	Effective, but studies show a slightly higher rate of acute rejection compared to tacrolimus, particularly in liver transplant patients.	Better at preventing acute rejection, particularly in liver and kidney transplant patients.

Conclusion: A Cornerstone of Modern Medicine

Since its approval in the 1980s, ciclosporin has revolutionized the field of transplant medicine by making long-term organ survival a reality for countless patients. As a calcineurin inhibitor, it specifically targets T-cell activation, offering a potent immunosuppressive effect used not only for transplants but also for managing severe autoimmune diseases. Its use requires a careful balance between achieving therapeutic effect and managing potential side effects, such as nephrotoxicity and an increased risk of infection. The development of modified formulations and a deeper understanding of its interaction profile have enhanced its clinical utility. While newer agents like tacrolimus exist, ciclosporin remains a vital component of the medical toolkit, especially when considering its distinct side effect profile and long-term history of efficacy.

For more detailed information, consult the National Institutes of Health (NIH) StatPearls article on Cyclosporine.

Frequently Asked Questions

Ciclosporin is primarily used to prevent the rejection of transplanted organs (kidney, liver, heart) and to treat severe autoimmune conditions like rheumatoid arthritis, psoriasis, and atopic dermatitis.

It is a calcineurin inhibitor that suppresses the immune system by preventing the activation of T-lymphocytes, which are responsible for attacking foreign tissues and initiating autoimmune responses.

Common side effects include increased hair growth, swollen gums, high blood pressure, headaches, kidney problems, and gastrointestinal issues like nausea and diarrhea.

No, you should avoid grapefruit and grapefruit juice while on ciclosporin, as it can interfere with the medication's metabolism and significantly increase blood levels, raising the risk of toxicity.

Modified ciclosporin (e.g., Neoral®, Gengraf®) is a microemulsion formulation that offers more consistent and reliable absorption than the older, unmodified version (Sandimmune®). They are not interchangeable and require different dosing.

No, ciclosporin and tacrolimus are different calcineurin inhibitors. While they have a similar mechanism, tacrolimus is generally more potent and has a different side effect profile, with a higher risk of post-transplant diabetes.

Yes, regular blood tests are crucial to monitor ciclosporin levels, as well as kidney function, to ensure the medication is effective and to minimize the risk of serious side effects.