IMMUNOMODULATORS AND THEIR RECEPTORS 393
Azathioprine, cyclophosphamide, methotrexate, leflunomide
“Lymphocyte-specific” cytotoxic agents
Mycophenolate mofetil- Agents (“small” molecules) that inhibit cytokine production or action
Corticosteroids
Prednisone, dexamethasone
Natural product derivatives
Cyclosporine, tacrolimus, sirolimus
Thalidomide - Agents (“small” molecules) that target cytokine receptors
- Cytokines
Interferons (IFN-β) - Antibodies that target lymphocytes or cytokine receptors
Of these five categories, the nonspecific cytotoxic agents and corticosteroids are the
most widely used clinically.
Although commonly employed as immunosuppressants, the cytotoxic agents are tradi-
tionally used to treat cancer. These drugs inhibit the growth of rapidly dividing cells. Since
blood cells, such as leukocytes or lymphocytes, tend to proliferate rapidly, they are prefer-
entially susceptible to cytotoxic agents. However, the majority of these agents (azathioprine
(6.1), cyclophosphamide (6.2), methotrexate (3.31)) are not specific for immune cells and
simply block the proliferation of all rapidly reproducing cells. Azathioprine is an imidazolyl
derivative of mercaptopurine and thus functions as an antimetabolite; cyclophosphamide is
an alkylating agent; methotrexate is a derivative of folic acid and functions as an antimetabo-
lite; and leflunomide (6.3) is a prodrug of an inhibitor of pyrimidine biosynthesis.