Cytokine is a type of protein that is made by certain immune and non-immune cells and has an effect on the immune system. Some cytokines stimulate the immune system and others slow it down. They can also be made in the laboratory and used to help the body fight cancer, infections, and other diseases. Examples of cytokines are interleukins, interferons, and colony-stimulating factors (filgrastim, sargramostim).

Cytokines are soluble proteins that act as communication signals between cells. In a nonspecific innate immune response, various cytokines may be released to stimulate production of chemical mediators or other cell functions, such as cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and chemotaxis.

When a cytokine binds to its target receptor, the effect can vary widely depending on the type of cytokine and the type of cell or receptor to which it has bound. The function of a particular cytokine can be described as autocrine, paracrine, or endocrine. In autocrine function, the same cell that releases the cytokine is the recipient of the signal; in other words, autocrine function is a form of self-stimulation by a cell. In contrast, paracrine function involves the release of cytokines from one cell to other nearby cells, stimulating some response from the recipient cells. Last, endocrine function occurs when cells release cytokines into the bloodstream to be carried to target cells much farther away.

Three important classes of cytokines are the interleukins, chemokines, and interferons. The interleukins were originally thought to be produced only by leukocytes (white blood cells) and to only stimulate leukocytes, thus the reasons for their name. Although interleukins are involved in modulating almost every function of the immune system, their role in the body is not restricted to immunity. Interleukins are also produced by and stimulate a variety of cells unrelated to immune defenses.

The chemokines are chemotactic factors that recruit leukocytes to sites of infection, tissue damage, and inflammation. In contrast to more general chemotactic factors, like complement factor C5a, chemokines are very specific in the subsets of leukocytes they recruit.

Interferons are a diverse group of immune signaling molecules and are especially important in our defense against viruses. Type I interferons (interferon-α and interferon-β) are produced and released by cells infected with virus. These interferons stimulate nearby cells to stop production of mRNA, destroy RNA already produced, and reduce protein synthesis. These cellular changes inhibit viral replication and production of mature virus, slowing the spread of the virus. Type I interferons also stimulate various immune cells involved in viral clearance to more aggressively attack virus-infected cells. Type II interferon (interferon-γ) is an important activator of immune cells.

Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.

How do immune system modulators work against cancer?

Immune-modulating agents are a type of immunotherapy that enhance the body’s immune response against cancer.

Types of immune-modulating agents include:

• Cytokines, which are proteins made by white blood cells. They play important roles in your body’s normal immune responses and in the immune system’s ability to respond to cancer.

  Cytokines that are sometimes used to treat cancer include:

  • Interferons (INFs). Researchers have found that one type of interferon, called INF-alfa, can enhance your immune response to cancer cells by causing certain white blood cells, such as natural killer cells and dendritic cells, to become active. INF-alfa may also slow the growth of cancer cells or promote their death.
  • Interleukins (ILs). There are more than a dozen interleukins, including IL-2, which is also called T-cell growth factor. IL-2 boosts the number of white blood cells in the body, including killer T cells and natural killer cells. Increasing these cells can cause an immune response against the cancer. IL-2 also helps B cells (another type of white blood cell) produce certain substances that can target cancer cells.

  Hematopoietic growth factors are cytokines that are used to reduce side effects from cancer treatment by promoting the growth of blood cells that are damaged by chemotherapy. They include:

  • Erythropoietin, which increases the production of red blood cells
  • IL-11, which increases the production of platelets
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which both increase the number of white blood cells. Boosting white blood cells reduces the risk of infections. G-CSF and GM-CSF can also enhance the immune system response against cancer by increasing the number of cancer-fighting T cells.


• BCG is a weakened form of the bacteria that causes tuberculosis. It does not cause disease in humans. BCG is used to treat bladder cancer. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer. BCG stands for Bacillus Calmette-Guérin.


• Immunomodulatory drugs (also called biological response modifiers) stimulate the immune system. They include:
  • Thalidomide (Thalomid®)
  • Lenalidomide (Revlimid®)
  • Pomalidomide(Pomalyst®)
  • Imiquimod (Aldara®, Zyclara®)

  Thalidomide, lenaliodomide, and pomalidomide cause cells to release IL-2. They also stop tumors from forming new blood vessels. Tumors need to form new blood vessels to grow beyond a certain size. These three drugs may also be called angiogenesis inhibitors.

  Imiquimod is a cream that you rub on the skin. It causes cells to release cytokines.

Which cancers are treated with immune system modulators?

Most immune-modulating agents are used to treat advanced cancer. Some are used to help manage side effects.

What are the side effects of immune system modulators?

Immune-modulating agents can cause side effects, which affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of immune-modulating agent you are getting, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Immune-modulating agents can cause flu-like symptoms, which include:

• Fever
• Chills
• Weakness
• Dizziness
• Nausea or vomiting
• Muscle or joint aches
• Fatigue
• Headache

Learn more about flu-like symptoms caused by cancer treatment.

Cytokines can also cause many serious side effects, such as:

• Trouble breathing
• Low or high blood pressure
• Severe allergic reactions
• Lowered blood counts, which can raise the risk of infections and cause bleeding problems
• Blood clots
• Problems with mood, behavior, thinking, and memory
• Skin problems, such as rash, burning at injection site, and ulcers
• Organ damage

BCG can also cause urinary side effects.

Thalidomide, lenalidomide, and pomalidomide can cause:

• Blood clots
• Nerve problems that lead to pain, numbness, tingling, swelling, or muscle weakness in different parts of the body.
• Birth defects, if used during pregnancy

Imiquimod can cause skin reactions.

Cytokine release syndrome is a condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and CAR-T cells. Cytokine release syndrome is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. Cytokines are immune substances that have many different actions in the body.

Signs and symptoms of cytokine release syndrome include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Most patients have a mild reaction, but sometimes, the reaction may be severe or life threatening.