Cytokines and Their Side Effects

Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. When released, they signal the immune system to do its job. Cytokines affect the growth of all blood cells and other cells that help the body's immune and inflammation responses. They also help to boost anti-cancer activity by sending signals that can help make abnormal cells die and normal cells live longer.

One specific type of cytokine is called a chemokine. A chemokine can make immune cells move toward a target. There are different kinds of chemokines, including interleukins, interferons, tumor necrosis factors, and growth factors.

Some cytokines can be made in a lab and are used to treat cancer. Some are used to help prevent or manage chemotherapy side effects. They are injected, either under the skin, into a muscle, or into a vein. The most common ones are interleukins and interferons.

Interleukins

Interleukins are a group of cytokines that act as chemical signals between white blood cells. Interleukin-2 (IL-2) helps immune system cells grow and divide more quickly. A man-made version of IL-2 is approved to treat advanced kidney cancer and metastatic melanoma. IL-2 can be used as a single drug treatment for these cancers, or it can be combined with chemotherapy or with other cytokines such as interferon-alfa.

Side effects of IL-2 can include flu-like symptoms such as chills, fever, fatigue, and confusion. Some have nausea, vomiting, or diarrhea. Many people develop low blood pressure, which can be treated with other medicines. Rare but potentially serious side effects include an abnormal heartbeat, chest pain, and other heart problems. Because of these possible side effects, if IL-2 is given in high doses, it must be done in a hospital.

Other interleukins, such as IL-7, IL-12, and IL-21, continue to be studied for use against cancer too, both as adjuvants and as stand-alone agents.

Interferons

Interferons are chemicals that help the body resist virus infections and cancers. The types of interferon (IFN) are named after the first 3 letters of the Greek alphabet:

• IFN-alfa
• IFN-beta
• IFN-gamma

Only IFN-alfais used to treat cancer. It boosts the ability of certain immune cells to attack cancer cells. It may also slow the growth of cancer cells directly, as well as the blood vessels that tumors need to grow.

IFN-alfa can be used to treat these cancers:

• Hairy cell leukemia
• Chronic myelogenous leukemia (CML)
• Follicular non-Hodgkin lymphoma
• Cutaneous (skin) T-cell lymphoma
• Kidney cancer
• Melanoma
• Kaposi sarcoma

Side effects of interferons can include:

• Flu-like symptoms (chills, fever, headache, fatigue, loss of appetite, nausea, vomiting)
• Low white blood cell counts (which increase the risk of infection)
• Skin rashes
• Thinning hair

These side effects can be severe and can make treatment with interferon hard for many people to tolerate. Most side effects don’t last long after the treatment stops, but fatigue can last longer. Other rare long-term effects include damage to nerves, including those in the brain and spinal cord.