38b.

Summarize drugs that modulate immune function (mechanism of action, clinical applications,
pharmacokinetics and toxicities.
Immunomodulation is modulation (regulatory adjustment) of the immune system. It has natural and human-
induced forms, and thus the word can refer to the following:
 Homeostasis in the immune system, whereby the system self-regulates to adjust immune responses to
adaptive rather than maladaptive levels (using regulatory T cells, cell signaling molecules, and so forth)
 Immunomodulation as part of immunotherapy, in which immune responses are induced, amplified,
attenuated, or prevented according to therapeutic goals

Immunomodulators are the active agents of immunotherapy. They are a diverse array of recombinant,
synthetic, and natural preparation

Class Example
Interleukins IL-2, IL-7, IL-12
Cytokines Interferons, G-CSF
Chemokines CCL3, CCL26, CXCL7
Immunomodulatory imide drugs Thalidomide
Other Cytosine phosphate-guanosine
oligodeoxynucleotides, glucans

Interleukins
 Aldesleukin is a cancer treatment drug. It is also known as interleukin 2 (IL-2) or by its brand name
Proleukin. It is a treatment for kidney cancer.

Cytokines
Recombinant cytokines are used for:
1. Anemia (EPO)
2. Bone-related conditions (BMP)
3. G-CSF – treat neutropenia in cancer patients
4. INF-alpha – Help C and multiple sclerosis
5. INF gamma – treat chronic granulomatous disease and osteoporosis

Immunomodulatory imide drugs are a class of immunomodulatory drugs (drugs that adjust immune
responses) containing an imide group.
Examples: thalidomide and analogues
There are three generations of IMiDs, with each successive generation being better tolerated and more active
against inflammatory and malignant conditions.
1. First generation — thalidomide
2. Second generation — lenalidomide and pomalidomide
3. Third generation — apremilast
Mechanism of action
 Known that they inhibit the production of tumour necrosis factor, interleukin 6 and immunoglobulin
G and VEGF (which leads to its anti-angiogenic effects), co-stimulates T cells and NK cells and
increases interferon gamma and interleukin 2 production.
 Their teratogenic effects appear to be mediated by binding to cereblon.
 Apremilast, on the other hand, inhibits PDE4
Indications:
 Myelodysplastic syndrome (precursor to AML)
 Erthyema nodosum
 Multiple myeloma
Adverse effects:
 Peripheral neuropathy
 Thrombocytopenia
 Anaemia
 Venous thromboembolism
 There may be an increased risk of secondary malignancies (AML)