Cytokines are proteins that act as messengers between cells, regulating immune responses and inflammation. Historically, the ability of cells and other body systems to send signals to and from each other has been attributed to the nervous and endocrine (hormonal) systems. More recently, it has become clear that individual or small groups of immune cells can actually send chemical signals to other neighboring cells. These chemical signals come in the form of small proteins called cytokines.
How Are Cytokines Produced?
“Cytokines are interactive chemicals, secreted by various cells in the body. In a broad sense their role is to control immune function,” said Daniel T. Fisher, PhD, an affiliate member in the Department of Surgery at Roswell Park Comprehensive Cancer Center, in Buffalo.
Cytokines are proteins made by individual cells to signal other cells. Because nearly every cell in the body can be a source for cytokines, more than 250 cytokines have been identified. Most of these are found within the immune system.
The term cytokine means “moving cell.” Originally, the most dramatic observation scientists made about cytokines was their movement. Although the most well-known cytokines act by sending signals between cell types of the immune system, cytokines can also be released from many different types of cells in the body, boosting or hindering the effects of other cytokines as well.
What Are the Different Types of Cytokines?
Since their discovery, the list of known cytokines continues to grow. This presents a challenge when trying to name and group cytokines, and some are considered subtypes of others.
Some of the common names for different cytokines are:
Lymphokines relay messages between cells.
Chemokines stimulate movement of immune cells to fight infections.
Monokines help mobilize an immune response.
Interferons signal white blood cells to multiply to fight invading germs and for other neighboring cells to cells to turn up their own antiviral defense.
Tumor necrosis factors encourage cell multiplication, changes in fat (lipid) metabolism, and even the death of some cells, such as tumor cells.
Colony stimulating factors regulate growth of the immune system cells, helping to restore or mobilize cells the body needs.
Interleukins help immune cells grow and divide more quickly.
What Role Do Cytokines Play in the Immune System?
Broadly speaking, the role of cytokines is to give other cells a “to do” list. Within the immune system, these tasks can include:
Rapid cell division so that specific white blood cells can grow and mature
Stimulating white blood cells to move toward an invader
Swelling of cell groups, called an inflammatory response
Reduction in swelling, known as an anti-inflammatory response
Activation of nerve cells to send pain signals to the brain
These responses are all normal when a patient is fighting an infection. “Various cytokines act as a warning system, helping cells prepare for an attack by an invader, like a virus, for example,” Dr. Fisher said. Cells are being mobilized to remove the invading pathogen and heal the damage that is done. In this manner, cytokines also participate in alerting the body through the nervous system that an infection is underway, by causing pain or discomfort.
How Do Cytokines Do Their Work?
In biology, it is common to use the analogy of a lock and key. In this scenario, the cytokine is the key whereas a specific receptor on the outside of a cell is the lock. Another way to think about it is that cytokines are proteins that are made by cells to tell other cells what to do. Once the signal is recognized, or when the key is in the lock, the cell responds by doing what it is “told” – multiply, move, swell, shrink, or release a signal of its own.
After the cytokine sends a message to a recipient cell, “it can attract more white blood cells; it could make them more active; it could make them more able to kill cancer cells or bacteria; or it can make them able to divide faster,” said Christina Annunziata, MD, PhD, senior vice president, Extramural Discovery Science, at the American Cancer Society.
A healthy immune response is a delicate yet consistent response that deals primarily with detecting a foreign invader and removing it from the body. If the immune system is not working as it should, the balance of cytokines can become skewed or even wildly altered, and that can cause problems.
How Do Pro-inflammatory and Anti-inflammatory Cytokines Differ?
Cytokines typically produce swelling in response to cell damage from an injury or infection. Cytokines that do this are called pro-inflammatory cytokines, and they are considered the activators of the immune system. This is important in the process of seeking out and removing the invading pathogen and/or beginning the healing process.
For example, pro-inflammatory cytokines can cause the nearby blood vessels to let more cells and fluids into an injured area. They can also cause the local population of white blood cells to multiply rapidly to fight an infection. Finally, they can trigger nerve fibers to send pain signals to the brain. The observed effect of all this is redness, swelling, heat, and discomfort.
When an injury or infection is on its way to being healed, a series of anti-inflammatory cytokines will then work to reverse the process that took place during the inflammatory response. You might think of them as the cytokines that deactivate the immune system.
What Conditions Are Related to Cytokines?
There is a link between cytokines and cancer. Although a certain level of pro-inflammatory cytokines is helpful, by promoting healing and fighting cancer, too many of the anti-inflammatory cytokines can “actually block the ability of the immune system to kill a cancer,” Dr. Annunziata explained. She went on to say that this is the basis of immunotherapy, where the goal is to reverse the overproduction of anti-inflammatory cytokines and “try to promote the immune cells to kill the cancer.”
Some cytokines can act directly on the cancer cells themselves or on the blood vessels that supply the cancer cells and encourage them to grow.
Cancer treatments can produce swelling of tissues and the constant overproduction of certain cytokines that may affect the ability to generate the usual immune response. If the swelling endangers health, a treatment of anti-inflammatory cytokines may be recommended.
Abnormal cytokine levels can also cause the immune system to turn on itself. For example, systemic lupus erythematosus is an autoimmune disorder that is caused by overproduction of several different cytokines that cause the immune system to become overly reactive to the body’s own cells.
How Are Cytokines Used in Cancer Treatment?
Cytokines may be used as a treatment for some diseases, including cancer, because these messengers are effective at marshalling the cells of the immune system to enhance a response that is weakening. However, using cytokines as treatment “is very tricky, as they have so many different effects,” Dr. Annunziata noted. “Sometimes they will be pro-inflammatory on one set of cells and anti-inflammatory on another set of cells,” she said. Their effects may also be very short-lived.
Interferon (types 1 and 2) and interleukin 2 (IL2) are cytokines that can be used in cancer treatment, “primarily to enhance the immune system to work against the cancer,” Dr. Annunziata said.
There are also antibody therapies that block cytokines. “So, for example, if the cytokine is causing a cancer to grow, we can give an antibody that will block that cytokine,” she continued.
A newer type of immunotherapy for cancer treatment is chimeric antigen receptor (CAR) T-cell therapy. People who get CAR T-cells need cytokines to grow the CAR T-cells to give them back to the patient.
What Is a Cytokine Storm?
Using cytokines for treatment can sometimes lead to serious side effects, so patients often need to be monitored very carefully. For example, “When giving IL2, the person needs to be in the intensive care unit, for careful monitoring,” Dr. Annunziata emphasized.
In some cases, when cytokines levels become highly elevated, they produce increasing symptoms such as fever, chills, low blood pressure, fast heart rate, and headaches,” Annunziata said. In a severe situation, a “cytokine storm” (the medical term is “cytokine release syndrome”) happens when the immune system’s normal response is thrown into overdrive. This is an infrequent occurrence, but it sometimes happens when the body responds way too strongly to an infection (like COVID-19, for example) or after some immunotherapy treatments.