Cyclosporine

Inside T cells, cyclosporine binds a carrier protein called cyclophilin. The drug-protein complex then blocks calcineurin, a calcium-dependent enzyme that T cells rely on to pass on the signal from their receptor². With calcineurin blocked, T cells make less interleukin-2 and other signaling molecules, which turns down the immune attack on a transplanted organ or on inflamed joints and skin³. The effect is reversible, falls mainly on helper T cells, and does not suppress the bone marrow³.

In the eye, the Restasis label describes it as a partial immunomodulator whose exact action is not known⁵. Neoral and Sandimmune are absorbed differently and cannot be swapped without a doctor's supervision; blood levels are monitored, and many drugs raise or lower them³.

The pivotal human evidence is old but substantial. In a 1983 randomized trial of 209 kidney-transplant recipients, predicted one-year graft survival was 80% with cyclosporine plus prednisone versus 64% with azathioprine-based therapy, though serum creatinine, a kidney-function marker, was higher and one lymphoma occurred in the cyclosporine group¹. Biochemical work in 1991 identified calcineurin as the shared target of the cyclosporine and tacrolimus (FK506) complexes, explaining how both drugs block T-cell signaling². For the eye, two identical 6-month randomized trials in 877 people with moderate to severe dry eye found cyclosporine emulsion improved corneal staining and tear-production (Schirmer) scores more than the vehicle alone⁴. Labels also cover severe rheumatoid arthritis and severe plaque psoriasis that has not responded to other treatment³.

FDA-approved since 1983 (Sandimmune), with Neoral and generics, to prevent rejection of kidney, liver and heart transplants and to treat severe rheumatoid arthritis and severe psoriasis^3,6. Eye-drop versions such as Restasis are approved to increase tear production when it is presumed to be suppressed by eye inflammation⁵.

The Neoral label carries a boxed warning: it raises the risk of infections and cancers, including lymphoma, and psoriasis patients with certain prior treatments face a higher risk of skin cancer. It can cause high blood pressure and kidney damage, more likely with higher exposure and longer use, so kidney function is monitored. Tremor, excess hair growth and gum overgrowth are among its principal side effects. Many drugs raise or lower its levels. With the eye drops, the most common effect is burning in the eye^3,5.

1. Canadian Multicentre Transplant Study Group, N Engl J Med 1983PubMed
2. Liu et al., Cell 1991PubMed
3. FDA label: NeoralFDA
4. Sall et al., Ophthalmology 2000PubMed
5. FDA label: Restasis MultiDoseFDA
6. Drugs@FDA: NDA 050573 (Sandimmune)FDA