Cytokines

BACKGROUND

Cytokines facilitate communication among immune cells, which fight against harmful substances, such as bacteria, that enter the body.

There are six major types of cytokines: chemokines, colony-stimulating factors, interferons, interleukins, transforming growth factors, and tumor necrosis factors (TNF). These cells help stimulate cellular reproduction, growth, and development. They are also involved in the body's response to injury, wound healing, immunity, and tolerance.

When cytokines are released, they bind to the receptors on the outside of their target cells. This action sends a chemical signal to the cell, stimulating it to perform a specific activity. For instance, during an infection, some cytokines stimulate immune cells to multiply. This helps the body fight against disease and infection.

Many different cells can produce the same cytokine. When a single cytokine stimulates many cells, it is called pleiotropy. When two or more cytokines work together, it is called synergism. When two or more cytokines produce opposite effects, it is called antagonism. These proteins are often produced in a cascade. In other words, when one cytokine is produced, this stimulates the production of many more cytokines.

TYPES OF CYTOKINES

Chemokines: Chemokines help immune system cells coordinate an attack against a foreign substance (such as a virus) that enters the body. Once a foreign substance has been identified in the body, white blood cells called macrophages release chemokines. The chemokines signal immune cells, such as T-lymphocytes and macrophages, to travel towards the infection and destroy the invading substance.

Colony-stimulating factors (CSF): Colony-stimulating factors (CSF) promote the production of white blood cells. There are two types of CSFs: granulocyte colony-stimulating factors and granulocyte-macrophage colony-stimulating factors.

Granulocyte colony-stimulating factors (G-CSF) stimulate the production of neutrophils, which are also called granulocytes. Neutrophils are especially important in fighting off infection and disease because they make up 70% of all white blood cells in the body. When a disease-causing microorganism enters the body, neutrophils are the first cells to begin engulfing the invader. When an invader is engulfed, it is no longer a threat to the body.

Granulocyte-macrophage colony-stimulating factors (GM-CSF) stimulate the production of both neutrophils and macrophages. Macrophages also have the ability to engulf foreign substances that enter the body.

Some patients receive CSF as part of medical treatment. For instance, a cancer treatment called chemotherapy weakens the body's bone marrow, which is responsible for producing immune cells. Some chemotherapy patients may receive CSF to stimulate the production of white blood cells. This subsequently boosts the immune system.

Interferons: Interferons help prevent viruses from replicating inside the body. Interferons stimulate natural killer (NK) T-cells to destroy body cells that have become infected with viruses or cancer. The NK T-cells have pouches, called granules, which are filled with chemicals that destroy infected cells on contact.

Interleukins: Interleukins are proteins that help regulate the inflammatory and immune responses by activating the body's white blood cells, such as T-lymphocytes. There are more than 20 known types of interleukins, which each have a unique function.

Transforming growth factors (TGFs): Transforming growth factors (TGFs) are proteins that stimulate cellular growth. There are two types of TGFs: transforming growth factor-alpha and transforming growth factor-beta. Transforming growth factor-alpha, which is produced by brain cells, macrophages, and keratinocytes, stimulates the growth of cells that line the outer surfaces of the body and organs. Transforming growth factor-beta stimulates tissue regeneration, cellular differentiation, embryonic development, and it also helps regulate the immune system.

Tumor necrosis factor (TNF): Tumor necrosis factor (TNF) is a protein that stimulates the destruction of some types of cancer cells in the body. While macrophages are the primary producers of TNF, other cells, including red and white blood cells and cells that line the blood vessels, also release TNF. When cancer cells are detected in the body, TNF is released into the blood. The TNF then binds to the cancer cell, causing changes in the cell that ultimately lead to cell death.

TNF has been combined with some cancer drugs to help treat skin cancer and sarcoma. Sarcoma is a type of cancer that develops in connective tissues like bone, cartilage, fat, blood vessels, muscle, tendons, or ligaments.

CYTOKINE STORM

A cytokine storm is a potentially fatal immune reaction in which the cytokines continue to stimulate the production of immune cells when they are no longer needed. The cause of this reaction remains unknown.

A cytokine storm may occur in response to an infection, such as pneumonia, or non-infectious conditions, such as graft-versus-host disease (complication of bone marrow transplant when the donated cells attack the recipient) and adult respiratory distress syndrome (lung injury that causes the lungs to become stiff, making it difficult to breathe).

Cytokine storms can cause significant damage to the body. For instance, if this reaction occurs in the lungs, fluids and immune cells may accumulate making it increasingly difficult for the patient to breathe.

Patients who experience this reaction will have elevated levels of all types of cytokines in their blood.

There is currently no standard treatment for cytokine storms. ACE inhibitors and angiotensin II receptor blockers have been suggested as possible treatments. However, further research is necessary to confirm their safety and efficacy.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• Fowler DH, Foley J, Whit-Shan Hou J, et al. Clinical "cytokine storm" as revealed by monocyte intracellular flow cytometry: correlation of tumor necrosis factor alpha with severe gut graft-versus-host disease. Clin Gastroenterol Hepatol. 2004 Mar;2(3):237-45. .View abstract
• Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007 May 1;117(5):1175-1183. .View abstract
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2007. Accessed May 23, 2007.
• Nunez-Naveira L, Montero-Martinez C, Ramos-Barbon D. Oxidation, inflammation and structural modifications.Arch Bronconeumol. 2007 May 9;43(Supl.1) [Epub ahead of print]. .View abstract
• Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006 Sep 7;355(10):1018-28. Epub 2006 Aug 14. .View abstract
• The International Society for Interferon and Cytokine Research. www.isicr.org. Accessed May 23, 2007.