Immunomodulating & Immunosuppressant Drugs

• Immunomodulating drugs establish harmony during immune system dysregulation
• Immunomodulating drugs are divided into immunostimulants and immunosuppressants
• Immunostimulants enhance specific immune system functions
• Immunosuppressants inhibit immune function

Immunosuppressants

• Glucocorticoids are the most clinically relevant and researched immunosuppressants
• Other immunosuppressants are used with glucocorticoids in specific medical situations
• These situations include reducing organ transplant rejection risk and stent stabilization for blood vessel occlusion
• Non-glucocorticoid immunosuppressants are categorized into four main classes: immunophilin binding drugs, cytostatic drugs, antilymphocyte antibodies, and monoclonal antibodies

Immunophilin Binding Drugs

• Immunophilins are cytosolic proteins catalyzing cis-trans isomerization for the amino acid proline
• Correct protein folding relies on this isomerization
• Immunophilins act as the receptor for this class of immunosuppressants
• Cyclosporin and tacrolimus are examples of immunophilin binding drugs
• After administration, the drug enters the cytosol of T-cells and binds with immunophilin
• The drug-immunophilin complex binds to calcineurin
• Calcineurin acts as a transcription factor to promote interleukin-2 production
• The immunophilin-drug complex inhibits interleukin-2 transcription by binding to Calcineurin
• Interleukin-2 is a pro-immune chemokine which increases T-cell activity, maturation, and differentiation
• Reduction in interleukin-2 production leads to immunosuppression
• Rapamycin inhibits interleukin-2 production via inhibition of the mTOR signaling pathway, and it is another immunophilin binding drug
• Immunophilin binding drugs are primarily used for immunosuppression after organ transplantation and to treat some autoimmune diseases

Cytostatic Drugs

• These drugs inhibit cell division to reduce the proliferation of T and B lymphocytes
• They reduce the rate of cell division by inhibiting DNA replication
• Methotrexate inhibits the enzyme dihydrofolate reductase resulting in in the inhibition of thymidine synthesis
• Thymidine is a critical deoxynucleoside for DNA synthesis and replication
• Similar drugs with immunosuppressive qualities are used to treat both immune system related cancers and autoimmune diseases
• Adverse effects in one treatment can be therapeutic for a different condition; cancer chemotherapy drugs have the adverse effect of immunosuppression, but in cases of immune-stimulating cancers, immunosuppressive qualities are therapeutic

Anti-lymphocyte Antibodies

• Alemtuzumab is an example, which binds to CD52, a glycoprotein on the surface of mature B and T lymphocytes triggering cell apoptosis
• By increasing apoptosis of lymphocytic cells, an immunosuppressive effect is achieved
• Alemtuzumab is used for the autoimmune condition multiple sclerosis and in some leukemias

Monoclonal Antibodies

• Muromonab is an example, which binds to the CD3 protein of the T cell receptor on T cells which triggers T cells apoptosis pathways leading to immunosuppression
• These drugs are often used in acute organ transplant rejection that are glucocorticoid resistant, as well as some T-cell related cancers such as T-cell acute lymphoblastic leukemia

Overview of immunomodulating drugs and their classification into immunostimulants and immunosuppressants. Focus on immunosuppressants, including glucocorticoids and immunophilin-binding drugs. Discusses clinical relevance and mechanisms of action.