Immunomodulators are medications that modify the body’s immune response. According to their main effect, immunomodulators can be subdivided into immunostimulants, which are used to enhance the immune response against a specific pathogen or cancer cell; and immunosuppressants, which include monoclonal antibodies used in the targeted treatment against certain types of cancer; and tyrosine kinase inhibitors used for diseases such as leukemias and gastrointestinal tumors.
Now, let’s begin with immunostimulants, which include interferons and interleukins, among other agents. Interferon medications mimic the effects of natural interferons, which are tiny proteins released by virally infected cells. As their name implies, they “interfere” with viral replication, thereby helping cells fight off viral infections. Additionally, they inhibit tumor growth and enhance the immune response.
Interferon medications can be administered subcutaneously or intramuscularly, and they include interferon alpha-2b, which can be used for the treatment of disorders like hairy cell leukemia or AIDS-related Kaposi sarcoma, as well as interferon beta-1a and interferon beta-1b, which can be used for the treatment of relapsing multiple sclerosis.
Moving on, interleukins are tiny signaling proteins that are similar to interferons; they communicate between cells to stimulate cellular immunity, inhibit tumor growth, and increase the production of platelets. One medication called aldesleukin is a human recombinant interleukin 2 agent, which means it acts like interleukin 2 would, promoting the proliferation and activity of various types of lymphocytes. Aldesleukin is administered intravenously, and can be used for treatment of metastatic melanoma or metastatic renal cancer.
However, overstimulation of the immune system can also cause side effects. Interferons, for example, can all cause neurotoxicity, which leads to side effects from headache and fatigue to anxiety, depression and, rarely, suicidal ideation. Interferons can also cause gastrointestinal toxicity, so nausea, vomiting, diarrhea or abdominal pain can commonly occur.
Other side effects include fever; injection site reactions; flu-like symptoms; dermatological side effects like rashes, pruritus or alopecia; musculoskeletal pain, including muscle soreness and joint pain; as well as fatigue and loss of appetite. Finally, remember that interferon alpha 2b and peginterferon alpha 2a have a boxed warning for causing or aggravating life-threatening neuropsychiatric, autoimmune, infectious and ischemic conditions.
On the other hand, aldesleukin has a boxed warning for capillary leak syndrome, which can cause severe, life-threatening hypotension and decreased organ perfusion. Other side effects of interleukins include gastrointestinal toxicity, fever, dyspnea, coughing, rashes and pruritus, as well as cardiac events like tachycardia, various types of arrhythmia and edema.
As far as contraindications go, interferons and interleukins are contraindicated in pregnant individuals and during breastfeeding. Additionally, interferons should be used with caution in clients with pre-existing cardiac disease, severe renal or hepatic impairment, myelosuppression, or compromised central nervous system function. Interleukins should be used with extreme caution in clients with cardiac arrhythmias, respiratory disorders, or renal or hepatic impairment.
Now, switching gears, immunosuppressants include a number of different medications, including monoclonal antibodies and tyrosine kinase inhibitors, which are used to regulate the immune system and target cancer cells.
All right, now monoclonal antibodies are easy to identify, because they all end in -mab. Examples include trastuzumab, which can be used for the treatment of certain types of breast or stomach cancers; as well as rituximab, which can be used for chronic lymphocytic leukemia and non-Hodgkin lymphoma; and infliximab, which can be used to treat inflammatory conditions like certain types of arthritis or inflammatory bowel disease. Monoclonal antibodies are administered intravenously. Once administered, they selectively bind to a specific antigen on the surface of the target cell, and then signal the immune system to destroy it.
On the other hand, there are tyrosine kinase inhibitors, which all end in -nib. These include imatinib and dasatinib, which can be used for the treatment of acute lymphoblastic leukemia. They’re both administered orally, and they act in a very similar way to monoclonal antibodies, with the difference that they can easily enter cells due to their low molecular weight. As a result, they can be used to target both extracellular receptors and intracellular proteins that regulate the growth and death of cancer cells.
Now let’s talk about the side effects! Common side effects of monoclonal antibodies include fever, fatigue, insomnia and headache, as well as cardiovascular reactions, like hypertension, flushing and edema; dermatological reactions like rashes, exfoliative dermatitis and pruritus; gastrointestinal toxicity, manifesting as nausea, diarrhea, abdominal pain or stomatitis; as well as muscle and joint pain.
They can also cause respiratory side effects like coughing and dyspnea, as well as hematologic disturbances, including anemia, thrombocytopenia and leukopenia. Trastuzumab also has a boxed warning for cardiomyopathy, infusion reactions, pulmonary toxicity, and pregnancy; and other specific side effects include decreased left ventricular ejection fraction and infections.
