Cyclosporine

Cyclosporines are drugs used in the field of immunosuppressant medicine to prevent the rejection of transplanted organs. They were discovered by Jean F. Borel in 1972. The cyclosporine used for transplant surgery is called cyclosporine A (CsA) and in 1984 it was added to the group of medicines used to prevent transplant rejection. Cyclosporine A is the most common form of the Norwegian fungus Tolypocladium inflatum.

The discovery of cyclosporine has led to a significant rise in the number of organ transplant operations performed as well as the rate of success. Cyclosporine has increased both the short- and long-term survival rates for transplant patients, especially in heart and liver operations. The rejection of grafted tissues occurs when white blood cells (lymphocytes) called T-helper cells stimulate the activity of cell-destroying (cytotoxic) T-killer cells. It is believed that cyclosporine interferes with the signals sent by the T-helper cells to the T-killer cells. These T cells , along with other white blood cells like monocytes and macrophages, cause the tissue rejection of the implanted organs.

Cyclosporine has proven to be the most effective medicine used to combat the body's own immune system , which is responsible for the rejection of transplanted organs. In addition to curtailing the activity of T-helper cells, cyclosporine is also able to fight the infectious illnesses that often occur after a transplant operation and can lead to death.

Cyclopsporine must be administered very carefully, since it can produce a number of toxic side effects, including kidney damage. Many clinical trials have been conducted using other drugs in combination with cyclosporine in an effort to reduce these side effects.

Immunosuppression

There are two types of immunosuppression: specific suppression and nonspecific suppression. In specific suppression, the blocking agent restricts the immune system from attacking one or a specific number of antigens (foreign substances). In nonspecific immunosuppression, the blocking agent prevents the immune system from attacking any antigen. Nonspecific immunosuppression, therefore, breaks down the ability of the body to defend itself against infections.

In the case of organ transplants, the recipient's body responds to the donor's organ tissues as if they were infecting foreign tissues. A drug that is a specific suppressing agent could block the immune system's antigenic response to the newly implanted organ. While specific suppression has been accomplished in animal transplants, it has not succeeded in human trials. So far, all the drugs used to suppress the immune system after an organ transplant are nonspecific suppressants.

In administering nonspecific immunosuppressants, a balance has to be maintained between the need for protecting the new organ from the immune system's attack (rejection) and the immune system's normal functioning, which protects the individual from infectious diseases. As time passes after the transplant operation, the body slowly begins to accept the new organ and the amount of immunosuppressant drugs can be decreased. If, however, the immunosuppressant is suddenly decreased shortly after the operation, larger doses may have to be given several years later to avoid rejection of the transplanted organ.

All the immunosuppressant drugs have side effects and individuals react to them in different ways. One strategy often used is to create a mix of the different drugs—usually azathioprine, cyclosporine, and prednisone—for the transplant patient. For example, a patient whose blood pressure is elevated by cyclosporine could take less of that drug and be introduced instead to prednisone. If an adverse reaction takes place with azathioprine, cyclosporine could replace it.

Administration

Cyclosporine can be taken either orally or by intravenous injection. While the injection reduces the amount of a dose by two-thirds, it can also produce side effects like kidney damage and other neural disturbances. As an oral preparation, it can be taken mixed with other liquids or in capsules. It is most effective when taken with a meal, since the digestive process moves it toward the smaller intestine, where it is absorbed.

In order to prevent rejection, many doses of cyclosporine have to be taken, usually starting with high dosages and then reducing them over time. The size of the dose is determined by the weight of the individual. Dosages also vary from one individual to another depending on the patient's ability to withstand organ rejection. Frequent blood tests are done on the patient to monitor all the factors that go into successful drug therapy.

Another problem for transplant patients is the cost of cyclosporine; a year's supply can cost as much as $6,000. Although medical insurance and special government funds are available to pick up the cost of this drug, the expense of the medication still poses a problem for many transplant patients.

Side effects

Aside from potential damage to the kidneys, there are a number of other side effects of cyclosporine. They include elevated blood pressure, a raise in potassium levels in the blood, an increase in hair growth on certain parts of the body, a thickening of the gums, problems with liver functioning, tremors, seizures, and other neurological side effects. There is also a small risk of cancer with cyclosporine as well as with the other immunosuppressant drugs.

See also Antibody and antigen; Transplant, surgical.

Resources

books

Auchinloss, Hugh, Jr., et al. Organ Transplants: A Patient'sGuide. Cambridge: H. F. Pizer, 1991.

Barrett, James T. Textbook of Immunology. St. Louis: Mosby, 1988.

Joneja, Janice V., and Leonard Bielory. Understanding Allergy,Sensitivity, and Immunity. New Brunswick: Rutgers University Press, 1990.

Sell, Stewart. Basic Immunology. New York: Elsevier, 1987.

Weiner, Michael A. Maximum Immunity. Boston: Houghton Mifflin, 1986.

periodicals

Kiefer, D. M. "Chemistry Chronicles: Miracle Medicines." Today's Chemist 10, no. 6 (June 2001): 59–60.

Jordan P. Richman

KEY TERMS

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Antigen

—A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.

Donor organ

—An organ transplanted from one person (often a person who is recently deceased) into another.

Macrophage

—A large cell in the immune system that engulfs foreign substances to dispose of them.

Organ recipient

—A person into whom an organ is transplanted.

T-helper cells

—Immune system cells that signal T killer cells and macrophages to attack a foreign substance.