**6.2 Cytostatics**

Cytostatics inhibit cell division. In immunotherapy, they are used in smaller doses than when used to treatment malignant diseases. They affect both T and B cell proliferation. As they are the most effective, purine analogs are most frequently administered.

#### *Alkylating agents*

The alkylating agents used in immunotherapy include cyclophosphamide (nitrogen mustards), nitrosoureas, platinum compounds, and others. Cyclophosphamide is probably the most potent immunosuppressive compound. In small doses, it is very efficient for the treatment of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis, and other immune diseases. However, high doses cause pancytopenia and hemorrhagic cystitis.

#### *Antimetabolites*

Methotrexate is a folic acid analogue. It binds dihydrofolate reductase and prevents the synthesis of tetrahydrofolate. In addition to its use in transplant patients, it is used for the treatment of autoimmune diseases such as rheumatoid arthritis and Behcet's disease.

It is extensively used to control transplant rejection reactions. Azathioprine is nonenzymatically cleaved to mercaptopurine, which acts as a purine analogue and an inhibitor of DNA synthesis. Additionally, mercaptopurine itself can also be administered directly.

By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It is also efficient in the treatment of autoimmune diseases.
