The use of immunosuppressive and cytotoxic drugs in non-malignant disease.

Cytotoxic drugs prevent cell division or cause cell death. They act predominantly on rapidly dividing cells such as T lymphocytes, and are therefore immunosuppressive and anti-inflammatory. When cytotoxic drugs were initially used in the treatment of cancer, it became apparent that they had profound eVects on the immune system. This “unwanted” side eVect has subsequently been exploited for the treatment of non-malignant disease where autoimmune mechanisms are considered important in the pathogenesis. More recently drugs such as cyclosporine, which act more specifically on the immune system via the inhibition of T lymphocyte function, are being used for the treatment of disease with immunologically mediated mechanisms. Generally speaking cytotoxic drugs (CDs) have anticancer activity as well as immunosuppressive properties, whereas immunosuppressive drugs (ISDs) show a more specific immunosuppressive eVect, although this distinction is partly arbitrary. For the purposes of this review we have adopted the classification described in the British National Formulary defining cyclosporine as an ISD; cyclophosphamide, vincristine, chlorambucil, and methotrexate as CDs; and azathioprine (and its active metabolite 6-mercaptopurine) and mycophenolate mofetil as “cytotoxic immunosuppressants”. This review concentrates on the use of ISDs and CDs in the management of vasculitis and rheumatological disease, idiopathic nephrotic syndrome, and inflammatory bowel disease. For the majority of the disorders discussed treatment with ISDs and CDs will usually be initiated by clinicians with experience of the condition. Reference to eYcacy and safety of ISDs and CDs in children will be made. Specifically, the use of ISDs and CDs in organ transplantation will not be addressed.