Immunosuppressant drugs

Immunosuppressant drugs are medications that reduce the ability of the immune system to recognize and respond to the presence of foreign material. Such drugs were developed and still have an important use as a means of ensuring that transplanted organs and tissues are not rejected by the recipient.

Rejection of transplanted organs or tissue is a natural reaction of a person's immune system. In a very real sense, the transplanted material is foreign and is treated, as would be an infectious microorganism. The immune system attacks and tries to destroy the foreign matter. Suppressing the immune system allows the transplanted material to be retained.

Drugs to suppress the immune system are available only with a physician's authorization. Some commonly prescribed drugs are azathioprine, cyclosporine, prednisolone, and tacrolimus. These can be taken orally, both in solid and liquid forms, or can be injected.

The main target of such immunosuppressant drugs are the white blood cells (which are also called lymphocytes). The main function of lymphocytes is to patrol the body and root out foreign material. Then these cells, in combination with other immune system components, destroy the foreign material.

Transplantation of animal kidneys into humans was tried in the early 1900s, and human-to-human transplant attempts were first made in 1933. These attempts were unsuccessful. It was not until the years of World War II that the immunological basis for these failures was deciphered. Then, Peter Medawar observed that a skin graft survived about a week before being rejected, but a subsequent graft was rejected much more quickly. This led him to propose that an immunological response was at play in the rejection of transplanted material. This led to the first successful transplant in 1954, when the kidney of one identical twin was transplanted to the other twin. In the twins, the absence of genetic differences in their tissues would eliminate an immunological response.

As the role of the immune system in transplantation failure became more clear, the use of compounds to suppress the immune system began in the 1960s. In the 1960s and 1970s, the antigenic basis of immune recognition of foreign and non-foreign tissue became evident. With these discoveries came the recognition that the suppression of the immune system could aid in maintaining transplanted tissue. Successful transplantation of the liver was achieved in 1963, of the heart and small bowel in 1967.

In the 1980s, cyclosporin was discovered and shown to be effective in maintaining transplanted material. The clinical use of cyclosporin became standard. By the end of that decade, the use of immunosuppressant drugs just prior to and forever after a transplant had boosted the one-year transplant success rate to more than 80 per cent for all transplants except for the small intestine. In the present day, the survival rate of a kidney transplant is 86 percent even after five years.

Immunosuppressant drugs have other uses as well. Suppressing the immune system can lessen the disfigurement caused by severe forms of skin disorders such as psoriasis. Other examples include rheumatoid arthritis, Crohn's disease (which is an ongoing inflammation of the intestinal tract) and alopecia areata (nonuniform hair loss). In such cases the use of immunosuppressant therapy needs to be evaluated carefully, especially when the condition is not life threatening. This is because the deliberate suppression of the immune system can leave the individual vulnerable to other infections. Also, the clotting of blood can be inhibited, which could produce uncontrolled bleeding.

Another potential risk in the use of immunosuppressant drugs involves the administration of vaccines. The use of vaccines is not advisable when immunosuppressant drugs are being used, especially vaccines that utilize living but weakened bacteria or a virus as the agent designed to elicit protection. The deliberately immunocompromised individual could develop the disease for which the vaccine is intended to prevent.

The same risk analysis applies to the possible side effects of immunosuppressant drugs, which can include a higher than normal risk of developing some kinds of cancer later in life. The link between immunosuppressant drugs and cancer is not yet clear. The link was assumed to be a consequence of the interference with the ability of the body to detect and respond to cancerous cells. Conversely, cancer development has been viewed as being due partially to a failure of the immune system. Yet people with acquired immunodeficiency system, whose immune systems are also compromised, do not show increased rates of cancer. Instead, immunosuppressant drugs such as cyclosporine may themselves encourage the development of cancer by activating a cellular factor that makes cells more invasive.

It is now well known that the deliberate suppression of the immune system carries risks. However, the risks of a side effect or developing another illness, is usually less than the immediate health risk associated with not suppressing the immune system.

See also Autoimmunity and autoimmune diseases; Immunodeficiency

immunosuppressive drug any of a variety of substances used to prevent production of antibodies . They are commonly used to prevent rejection by a recipient's body of an organ transplanted from a donor. A transplant is rejected when the recipient's immune system acts against it; current methods aim at suppressing the activity of the lymphocytes, the cells that form antibodies (see immunity ; transplantation ). The steroids , such as cortisone , which suppress the antibody-forming lymphocyte cells, have been used to prolong human organ transplants. Steroids may also prevent antigens from entering cells and thereby prevent local allergic inflammation reactions. In another immunosuppressive method, human lymphocytes are injected into horses, stimulating the animals to produce antilymphocyte serum. The serum, administered to humans with transplanted organs, in some way inactivates lymphocyte cells. The procedure will not work effectively for more than a few injections of serum. Another group of immunosuppressive drugs act by interfering with the synthesis of nucleic acids and are especially effective against proliferating cells such as stimulated lymphocytes. Some of these are analogs of purines and pyrimidines, substances that are nucleic acid subunits; the purine analog azothioprine has been used to suppress rejection of transplanted human kidneys. Most substances that inhibit nucleic acid synthesis, such as nitrogen mustard , cyclophosphamide ( Cytoxan ), chloramphenicol , actinomycin , and colchicine , are not widely used clinically because they are too toxic. Many of the drugs that suppress the function of the immunological system are also used clinically to check growth of cancerous tissue, which is composed of rapidly dividing cells. The drugs currently used to suppress antibody formation also leave an individual susceptible to infection.

immunosuppressant (im-yoo-noh-sŭ-press-ănt) n. a drug, such as azathioprine or ciclosporin, that reduces the body's resistance to infection and other foreign bodies by suppressing the immune system. Immunosuppressants are used to maintain the survival of organ and tissue transplants and to treat various autoimmune diseases (see disease-modifying antirheumatic drug). Side-effects include increased susceptibility to infection due to damage to the blood-forming cells of bone marrow.

im·mu·no·sup·pres·sion / ˌimyənōsəˈpreshən; iˌmyoō-/ • n. Med. the partial or complete suppression of the immune response of an individual. It is induced to help the survival of an organ after a transplant operation. DERIVATIVES: im·mu·no·sup·pres·sant / -səˈpresənt/ n. im·mu·no·sup·pressed / -səˈprest/ adj.

immunosuppression The suppression of an immune response. Immunosuppression is necessary following organ transplants in order to prevent the host rejecting the grafted organ (see graft); it is artificially induced by radiation or chemical agents that inhibit cell division of lymphocytes. Immunosuppression occurs naturally in certain diseases, notably AIDS.

immunosuppressive drug Any drug that suppresses the body's immune responses to infection or ‘foreign’ tissue. Such drugs are used to prevent rejection of transplanted organs and to treat autoimmune disease and some cancers.

immunosuppression (im-yoo-noh-sŭ-presh-ŏn) n. suppression of the immune response, usually by disease (e.g. AIDS) or by drugs (e.g. steroids, azathioprine, ciclosporin).
—immunosuppressed adj.

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