The Paradox of Cytokines--Immune System Friends or Foes?

The Paradox of Cytokines--Immune System Friends or Foes?
by Elaine Moore
September 23, 2000
The Good
Despite their ominous sounding name, cytokines are merely protein hormone-like substances which act as immune system messenger molecules. Cytokines allow immune systems cells and organs to communicate with one another, and cytokines regulate the intensity of the immune response. In a sense, you could say that when it comes to immunity and autoimmunity, cytokines are responsible for knowing what's really going on and keeping the immune ball rolling. In fact, without a cascade of events where one type of cytokine, IL-2 produces another type of cytokine,IL-4, the body couldn't even produce antibodies.
Cytokines are soluble molecules secreted by immune system cells in response to a foreign threat. Cytokine secretion usually only last for a few hours to a few days. Unlike hormones, cytokines generally only affect organs and cells in their general vicinity and they only affect cells which have cytokine receptors.
The cytokine family is immense and includes at least 18 different interleukin (IL) compounds, plus numerous interferons (IFN), chemokines, and other proteins such as tumor necrosis factor (TNF). The effects of cytokines are varied and appear to depend on the particular cell which they activate. Also similar cytokine compounds can have entirely different functions. Cytokines can be synergistic, complementing and facilitating activity or they may be antagonistic, inhibiting signals.
Cytokines can be classified according to their primary biologic effects. Many cytokines influence hematopoiesis (the production of blood cells and platelets in the bone marrow. In particular, interleukin-3 (IL-3) stimulates stem cells to develop into specific types of blood cells. Another important cytokine is erythropoietin (EPO) which stimulates the production of red blood cells. As we'll later learn, EPO plays a valuable role in the treatment of anemia.
Many cytokines present in the circulation are involved in the inflammatory response. Inflammation, as part of the immune response, is good, bringing large forces of white cells to confront the enemy. In fact, imflammation is a major step in the healing process. IL-1, in particular, acts locally to attract white blood cells and systemically to induce a fever response via the hypothalamus. While all of the interferons can inhibit or interfere with the replication of viruses, interferon-gamma (IFN-g) also increases the surface expression available to the immune system's genes facilitating antibody production.
The Bad
So far, so good. But cytokines can overreact, in their efforts to fight foreign invaders. Then, they cause continued cell destruction. Septic or toxic shock induced by bacterial infections or toxins are actually caused by high levels of inflammatory cytokines produced in response to bacterial products. Adult T cell leukemia associated with HTLV-1 is characterized by the continuous production of IL-2. In organ transplant reactions, this over-production of IL-2 drives the rejection of transplanted tissue. Myeloma cells, a type of malignant B cell, are dependent on IL-6 for their growth. In Hashimoto's disease and atrophic thyroiditis, cytokines contribute to thyroid cell destruction.
Studies show that an imbalance of cytokines, particularly those that regulate each other, may contribute to the development and persistence of autoimmune disease. Recent studies show that certain tumor necrosis factor cytokines contribute to the symptoms seen in systemic lupus erythematosus.
The Beneficial
The nature of cytokines makes them excellent therapeutic agents. Granulotye/macrophage-colony stimulating factor (GM-CSF)and EPO (previously mentioned) are both used to induce production of white and red blood cells respectively. Alpha interferon is used to treat both hepatitis B and C infections as well as chronic myelogenous leukemia, non-Hodgkin's lymphoma and the AIDS-associated cancer known as Kaposi's sarcoma. Beta interferon is the first drug which has caused improvement in patients with multiple sclerosis. It's likely that in the future the use of cytokines in autoimmune disease treatment will expand as they are the focus of many ongoing clinical trials.
Monoclonal antibodies, in particular, produced against certain cytokines can neutralize them, blocking their destructive effects and inhibiting specific disease symptoms.

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