Immunology · Transplant, tumors and immunotherapy

Immunosuppressants by mechanism (classes) !

Topic

Medicines that calm the immune system to protect a transplant or control autoimmune disease, at the cost of more infections.

Updated 2026-11-01

Key points

Calcineurin inhibitors: cyclosporine (binds cyclophilin) and tacrolimus (binds FKBP12) block NFAT and IL-2 transcription; nephrotoxic, raise blood pressure, cause tremor; tacrolimus causes post-transplant diabetes; cyclosporine causes gingival hyperplasia and hirsutism.
mTOR inhibitors: sirolimus and everolimus bind FKBP12 and block the response to IL-2; not nephrotoxic, but cause hyperlipidemia, cytopenias, mouth ulcers and slow wound healing.
Antimetabolites: mycophenolate inhibits IMPDH (lymphocyte purine synthesis) and is teratogenic; azathioprine is a 6-mercaptopurine prodrug, toxic with low TPMT activity and with allopurinol.
Calcineurin inhibitors and mTOR inhibitors are CYP3A4 substrates: grapefruit and many drugs change their levels, so blood levels are monitored.
Long-term risks: opportunistic infections (CMV, Pneumocystis, BK virus), skin cancer and EBV-driven post-transplant lymphoproliferative disorder.

What it is

Immunosuppressants block T-cell activation at different points: cytokine gene transcription, the calcineurin–IL-2 pathway, the mTOR growth signal, DNA synthesis in dividing lymphocytes, or costimulation. Transplant regimens combine drugs from different classes to protect the graft with less toxicity from each. All raise the risk of infection and of some cancers.

Immunosuppressants by class

Class	Examples	Target and mechanism	Key adverse effects
Glucocorticoids	Prednisone, methylprednisolone	Block NF-κB and cytokine gene transcription; lower lymphocytes and eosinophils	Hyperglycemia, osteoporosis, Cushing features, mood change, infection, adrenal suppression
Calcineurin inhibitors	Cyclosporine, tacrolimus	Inhibit calcineurin, so NFAT cannot enter the nucleus and IL-2 is not made	Nephrotoxicity, hypertension, tremor, hyperkalemia; tacrolimus: diabetes; cyclosporine: gingival hyperplasia, hirsutism
mTOR inhibitors	Sirolimus, everolimus	Bind FKBP12 and block mTOR, stopping T-cell proliferation in response to IL-2	Hyperlipidemia, thrombocytopenia, mouth ulcers, poor wound healing, pneumonitis
Antimetabolites	Mycophenolate, azathioprine, methotrexate	Block purine (IMPDH, 6-MP) or folate pathways in dividing lymphocytes	Bone marrow suppression, GI upset; mycophenolate is teratogenic; azathioprine with allopurinol or low TPMT
Costimulation blocker	Belatacept, abatacept (fusion proteins, -cept)	CTLA-4-Ig binds CD80/CD86 (B7) and blocks the CD28 second signal	Post-transplant lymphoproliferative disorder in EBV-negative recipients (belatacept), infections
Induction antibodies	Basiliximab, antithymocyte globulin, alemtuzumab	Anti-CD25 (IL-2 receptor α); polyclonal T-cell depletion; anti-CD52	Infusion reactions, cytopenias, profound immunosuppression (depleting agents)
Alkylating agent	Cyclophosphamide	Cross-links DNA, kills dividing B and T cells	Hemorrhagic cystitis, myelosuppression, infertility, bladder cancer

Markers

Calcineurin
NFAT
IL-2
FKBP12
Cyclophilin
mTOR
IMPDH
CD80/CD86

Clinical notes

A typical solid-organ maintenance regimen combines a calcineurin inhibitor, an antimetabolite and a corticosteroid.
Prophylaxis against Pneumocystis and CMV is common in the first months after transplant.
Patients on these drugs are advised to protect their skin from the sun because of the high skin cancer risk.

Test yourself

Think of the answer, then tap the question to see it.

How do cyclosporine and tacrolimus suppress T cells?

They bind cyclophilin or FKBP12 and inhibit calcineurin, so NFAT cannot activate the IL-2 gene.

Which immunosuppressant class is not nephrotoxic but causes hyperlipidemia and poor wound healing?

mTOR inhibitors (sirolimus, everolimus).

Why is allopurinol dangerous with azathioprine?

Allopurinol blocks xanthine oxidase, which breaks down 6-mercaptopurine; levels rise and cause severe bone marrow suppression.

Which immunosuppressant inhibits IMPDH and is strongly teratogenic?

Mycophenolate.

Which cancer linked to EBV is a classic risk of long-term transplant immunosuppression?

Post-transplant lymphoproliferative disorder (PTLD), mostly B-cell lymphomas driven by EBV.

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Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: Tacrolimus (MedlinePlus Drug Information, U.S. National Library of Medicine, 2026); Mycophenolate (MedlinePlus Drug Information, U.S. National Library of Medicine, 2026); Transplant rejection (MedlinePlus, U.S. National Library of Medicine, 2026).

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