Principles of immunopharmacology

Where immunosuppressants and biologics act, how to read their names, why they raise infection and cancer risk, and what to check before starting them.

Updated Nov 2, 2026

Immunosuppressive and immunomodulating drugs prevent transplant rejection and control autoimmune and inflammatory disease. They act at different steps of T-cell and B-cell activation or on the cytokines that sustain inflammation. Their shared price is a weaker defence against infection and, with some, against cancer.

Key points

T-cell activation has three signals: antigen on MHC, costimulation, and cytokine-driven proliferation; drugs block each one.
Calcineurin inhibitors (tacrolimus, ciclosporin) stop IL-2 production; mTOR inhibitors block the proliferation signal; antimetabolites (mycophenolate, azathioprine) stop lymphocytes from copying DNA.
Biologic names carry their structure: «-cept» is a receptor fusion protein; older «-mab» names show the source (-ximab chimeric, -zumab humanised, -umab human); new WHO stems (-tug, -bart, -ment, -mig) replace «-mab» for new antibodies.
Before strong immunosuppression, screen for latent tuberculosis and hepatitis B, and update vaccines: live vaccines are avoided once immunosuppressed.
Many oral immunosuppressants have narrow therapeutic windows and CYP3A4 interactions, so blood levels are monitored.

Where the drugs act

Signal 1 (antigen recognition): anti-CD3 and anti-thymocyte antibodies in transplantation
Signal 2 (costimulation): abatacept blocks CD80/86
Signal 3 (IL-2 and proliferation): calcineurin inhibitors, IL-2 receptor antibodies (basiliximab), mTOR inhibitors (sirolimus, everolimus)
DNA synthesis: mycophenolate, azathioprine, methotrexate
Cytokines: TNF, IL-6, IL-17, IL-23 and IL-1 blockers; JAK inhibitors block many cytokine signals inside the cell
Broad: corticosteroids act on many genes in many cells

Reading biologic names

The WHO International Nonproprietary Name scheme builds names from parts. Under the older scheme, «-mab» marks a monoclonal antibody and the letters before it show its origin: infliximab (chimeric), tocilizumab (humanised), adalimumab (human). «-cept» marks a receptor or other protein fused to an antibody fragment, such as etanercept and abatacept. In 2022 the WHO replaced «-mab» for newly named antibodies with four stems by structure: -tug (unmodified), -bart (engineered constant region), -ment (fragments) and -mig (bi- or multispecific).

Shared risks

Infections: common bacteria and viruses, plus opportunists (Pneumocystis, cytomegalovirus, fungi); reactivation of latent tuberculosis with TNF inhibitors and of hepatitis B with several agents
Cancer: lymphoma and skin cancer rise with long, intense immunosuppression (the tacrolimus label warns of lymphoma)
Live vaccines can cause disease in immunosuppressed people
Drug-specific toxicity: kidney injury and hypertension (calcineurin inhibitors), marrow suppression (antimetabolites), mouth ulcers and poor wound healing (mTOR inhibitors)

Practical principles

Tacrolimus, ciclosporin and sirolimus are broken down by CYP3A4 and moved by P-glycoprotein, so inhibitors (azoles, macrolides, grapefruit) raise their levels and inducers (rifampicin, some antiseizure medicines) lower them; trough levels guide therapy. Azathioprine is inactivated partly by TPMT, and gene testing helps avoid marrow toxicity. CDC guidance asks that indicated vaccines be given before immunosuppression starts whenever possible, with live vaccines withheld during it.

Tolerance: the goal

Immunosuppression damps all immune responses; tolerance would switch off only the unwanted one. Regulatory T cells, costimulation blockade and induction strategies in transplantation all aim at this, but lifelong drugs are still the rule for most transplant recipients.

Test yourself

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

How do calcineurin inhibitors suppress T cells?

They block calcineurin, so the transcription factor NFAT cannot enter the nucleus and IL-2 is not produced.

What does the suffix «-cept» mean in a drug name such as etanercept?

It is a fusion protein: a receptor (or other binding protein) joined to part of an antibody, usually the Fc fragment.

Why is latent tuberculosis screened before starting a TNF inhibitor?

TNF is needed to keep tuberculosis granulomas contained; blocking it can reactivate latent infection.

Why does clarithromycin raise tacrolimus levels?

It inhibits CYP3A4 (and P-glycoprotein), which normally clear tacrolimus.

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Example drugs

Connections

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Tacrolimus: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Altered Immunocompetence (Centers for Disease Control and Prevention (CDC), 2024); New INN monoclonal antibody (mAb) nomenclature scheme (May 2022) (World Health Organization, 2022).

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