Immunosuppressive Agents

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Major classes of agents employed in immunosuppressive therapy:
  • Corticosteroids
  • Cytotoxic Agents
  • T-cell suppressive agents
  • Antibodies

Mechanism of action:

  • Cytotoxic Agents- suppress bone marrow function

1. Cyclophosphamide:
a. Primarily suppresses B-cell production; lowers humoral immunity
b. Used to treat severe rheumatoid arthritis
c. Not normally used for graft rejection
2. Azathioprine
a. Primarily suppresses T-cell production
b. Used for graft rejection
c. Normally used in combination with corticosteroids
3. Mycophenolate Mofetil (CELLCEPT)
a. Mechanism of action: inhibits inosine monophosphate dehydrogenase; an
enzyme required for de novo purine synthesis
b. Selective because T and B cells rely on de novo pathway
c. Suppresses lymphocyte proliferation and B-cell antibody production
d. Can be used to inhibit transplant rejection

  • T-Cell Suppressor Agents

1. Cyclosporine and Tacrolimus
a. Mechanism of action: block proliferative response of T-cells to antigen by inhibiting calcineurin activity.
b. Have little myelotoxicity
c. Used in combination with corticosteroids for organ transplants
d. Variable oral absorption
e. Extensively metabolized
f. Metabolite excreted in urine
g. Cause renal toxicity in up to 75% of patients; frequently responsible for stopping therapy.

  • Antibodies

Selective antibodies against lymphocytes and thymocytes have been used as immunosuppressants.

1. Antithymocyte Globulin
(A) Polyclonal antibody, binds T-lymphocytes
(B) Primary use: graft rejection during acute phase
(C) Side effects: allergic reactions; consequences of immune suppression
b. Muromonoab-CD3
(A) Monoclonal antibody, binds to T-lymphocytes
(B) Primary use: acute graft rejection
(C) Side effects: cytokine release syndrome (can be fatal); allergic reactions; consequences of immune suppression.

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