Selective Cytokine Inhibitors

Cytokine inhibitors work by reducing inflammatory cytokines to exert their effect in treating inflammatory disorders and to weaken the immune system for transplant patients to avoid transplant rejection.  

Belatacept is used post-kidney transplant in combination with other medications. Belatacept binds CD80 and CD86 on antigen presenting cells (APCs), which blocks stimulation of T-cells. Limiting T-cell stimulation reduces downstream production of cytokines and T-cell proliferation.

Cyclosporine is used in liver, kidney, and heart transplants. Cyclosporine enters T-cells to binds and inactivate calcineurin. Calcineurin typically activates NFATc, cytosolic nuclear factor of activated t-cells, which promotes production of cytokines.

Everolimus and sirolimus are used in kidney transplant patients. Everolimus and sirolimus are mTOR inhibitor (serine/threonine kinase). Inhibition of mTOR, decreases T-cell proliferation as mTOR inhibition stops progression of activated T-cells.

Tacrolimus is used after variety of organ transplants for immune suppression.  Tacrolimus decreases cytokine production by binding FKBP-12, which binds calcineurin, which in turn can no longer activate NFATc, which would typically result in production of cytokines.

Class Drugs

• Belatacept

• Cyclosporine

• Everolimus

• Sirolimus

• Tacrolimus

Class Mechanism of Action

• See individual drugs

Class Applications

• See individual drugs

Class Adverse Effects

• See individual drugs

Drug Table

Drug Name	Application	Comments	Image
Belatacept	Immunosuppressant used in kidney transplants in combination with other immunosuppressants	Mechanism; -Binds CD80 and CD86 on antigen presenting cells (APCs), which blocks stimulation of T-cells; -Limits downstream production of cytokines and T-cell proliferation; Adverse Effects; -Posttransplant immunoproliferative disorder; -Associated with prior exposure with Epstein-Barr virus; -Contraindicated in seronegative EBV patients	"Bell" "Scepter"
Cyclosporine	Liver, kidney, and heart transplants	Mechanism; -Decreases production of cytokines; -Enters T-cells and binds and inactivates calcineurin; -Calcineurin typically activates a factor (NFATc - cytosolic nuclear factor of activated t-cells), which promotes production of cytokines; Adverse Effects; -Nephrotoxic, avoid using other nephrotoxic drugs concurrently; -Hepatotoxic; -Hirsutism; -Gingival hyperplasia	"Bicycle" "Spore"
Everolimus	Kidney transplant	Mechanism; -mTOR inhibitor (serine/threonine kinase); -Decreases T-cell proliferation as mTOR inhibition stops progression of activated T-cells; Adverse Effects; -Hyperlipidemia; -Angioedema; -Venous and arterial thrombosis of graft	"Everest" "Lime"
Sirolimus	Kidney transplant	Mechanism; -mTOR inhibitor (serine/threonine kinase); -Decreases T-cell proliferation as mTOR inhibition stops progression of activated T-cells; Adverse Effects; Hyperlipidemia	"Sir" "Lime"
Tacrolimus	Liver transplant; Kidney transplant; Pancreas transplant; Heart transplant; Dermatitis	Mechanism; -Decreases cytokine production; -Binds FKBP-12, which binds calcineurin, which in turn can no longer activate NFATc, which would typically result in production of cytokines; Adverse Effects; -Nephrotoxic; -Neurotoxic; -Increases risk of diabetes	"Tac" "Row" "Lime"