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was claimed to kill cancer cells but not normal cells. Although it was claimed that laetrile had no toxic effects, an 11-month-old girl died after swallowing tablets (1-5) being used by her father. The toxicity was due to metabolic formation of hydrocyanic acid in the intestine. There is no serious evidence that laetrile is effective.

As has so often been the case in the past, and no doubt will continue to be in the future, the calm evaluation of such claims is obstructed by a mixture of emotionalism and exploitation.

Interestingly, despite criticism of overpermissive laxity of the drug regulatory authority (FDA) in the USA, the public is unwilling to accept the opinion of the FDA when it advises against the use of drugs such as laetrile. It is important that these interventions be tested for efficacy and toxicity in the same way as conventional drugs are subject to rigorous clinical trials.

There is a long and generally dishonourable history of the promotion of cancer 'cures', but as each new one appears the medical profession must yet again be willing to look dispassionately at the possibility that this time there really may be something in it, whilst avoiding the tragic raising of hopes that will not be realised — a sad and difficult task.

Suppression of immune responses mediated via mononuclear cells (lymphocytes, plasma cells) is used in therapy of:

• Autoimmune and collagen and connective tissue disease (see below)

• Organ transplantation; to prevent immune rejection.

Cytotoxic cancer chemotherapeutic agents are immunosuppressive because they interfere with mononuclear cell multiplication and function. But they are generally too toxic for the above purposes and the following are principally used for intended immunosuppression:

10 Editorial. British Medical Journal 1977 1: 3.

• Adrenocortical steroids

• Azathioprine (see below)

• Ciclosporin, tacrolimus (see below)

• Some alkylating agents: cyclophosphamide and chlorambucil (see Table 30.2)

• Antilymphocyte immunoglobulin (see below).

With the exception of Ciclosporin and tacrolimus, all the above cause nonspecific immunosuppression so that the general defences of the body against infection are impaired.

Adrenal steroids destroy lymphocytes, reduce inflammation and impair phagocytosis (see Ch. 34).

Cytotoxic agents destroy immunologically competent cells. Azathioprine, a prodrug for the purine antagonist mercaptopurine, is used in autoimmune disease because it provides enhanced immunosuppressive activity. Cyclophosphamide is a second choice. Bone marrow is depressed as is to be expected.

Ciclosporin

Ciclosporin is polypeptide obtained from a soil fungus. It acts selectively and reversibly by preventing the transcription of interleukin-2 and other lymphokine genes, thus inhibiting the production of lymphokines by T-lymphocytes (that mediate specific recognition of alien molecules). Ciclosporin spares nonspecific function, e.g. of granulocytes, that are responsible for phagocytosis and metabolism of foreign substances. It does not depress haemopoiesis.

Pharmacokinetics. Ciclosporin is about 40% absorbed from the gastrointestinal tract and is extensively metabolised in the liver mainly by the cytochrome P450 3A system; the i'/2 is 27 h.

Uses. Ciclosporin is used to prevent and treat rejection of organ transplants (kidney, liver, heart-lung) and bone marrow transplants. It may be given orally or i.v. In the context of transplantation, administration continues indefinitely and must be carefully monitored, including measurement of plasma concentration and renal function. It is generally stopped after 6 months in patients who have received a bone marrow transplant unless there is ongoing chronic graft-versus-host disease.

Ciclosporin may also be used for severe, resistant psoriasis in hospitalised patients.

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