Interferons

Definition

Interferons are a group of proteins called cytokines produced by white blood cells, fibroblasts, or T-cells as part of an immune response to a viral infection or other immune trigger. The name of the proteins comes from their ability to interfere with the production of new virus particles.

Purpose

Interferons affect the immune system in a number of ways. For example, interferon beta can enhance the activity of lymphocyte cells while simultaneously inhibiting other immune cells from becoming stimulated. Additionally, interferon beta regulates the production of interferon gamma. Interferons can also inhibit viruses from establishing an infection inside human cells. Interferon alfa displays anti-tumor activity.

The exact molecular details of how interferons act is still unclear. They may make surface-exposed antigens of tumors even more capable of stimulating the immune system, which in turn would elicit a greater response from the T-cells of the immune system. Tumor growth may also be slowed or retarded by interferon-mediated damage to the blood cells that supply the tumor with nourishment.

Description

There are three types of interferons: alfa, beta, and gamma. Alfa and beta interferons, which are grouped together as type I interferon, are produced by white blood cells and a type of connective tissue cell called a fibroblast. Gamma interferon (or type II interferon) is manufactured T-cells. Production occurs when the T-cells are activated such as during an infection.

The alfa and beta interferons share some biological activities, but also have activities that are distinct from one another. These similarities and differences reflect the common and different binding of the interferons to various targets (receptors) on the surfaces of human cells.

Alfa interferon is manufactured by Roche Products (trade name Pegasys) and Schering-Plough (Viraferon-Peg). Biogen (Avonex) and Serono (Rebif) both market an interferon-designated beta-1a. Both of the beta-1a interferons are produced in genetically engineered mammals. For example, Rebif is produced in Chinese hamster ovary cells that contain the gene coding for human interferon beta.

An interferon designated as beta-1b enhances the activity of T-cells, while simultaneously reducing the production cytokines that operate in the inflammatory response to infection and injury. As well, this interferon retards the exposure of antigens on the surface of cells (and so lessens the development of an immune response to the antigens), and retards the appearance of white blood cells (lymphocytes) in the central nervous system.

The reduction of the immune response can lessen the damage to nerve cells in diseases such as multiple sclerosis. In this disease, the immune system is stimulated to react against the myelin sheath that surrounds the cells, a phenomenon called demyelination. Demyelination produces a malfunction in the transmission of impulses from nerve to nerve and from nerve to muscle.

Infection with the virus that causes hepatitis C is hindered by interferon via the binding to a site on human cells that is also used by the virus. Thus, the virus cannot enter and infect the host cell.

In the late 1980s, a large clinical trial conducted in the United States and Canada evaluated the influence of interferon beta-1b (Betaseron, marketed by Berlex) made in bacteria using genetic engineering technology. Specifically, the bacterium Escherichia coli contained a piece of genetic material (plasmid) that contains the gene coding for human beta interferon. The study was double-blind (neither the test participants or the researchers knew which person was receiving the real drug or a placebo). The two-year study demonstrated that those people receiving the interferon had fewer reappearances of the symptoms, and fewer nerves in the brain were damaged.

Betaseron was approved in 1993 by the U.S. Food and Drug Administration for use by people affected with multiple sclerosis. Avonex was approved in 1996 and Rebif in 2002.

Recommended dosage

Interferons are normally injected. They are not taken by mouth as the strong digestive enzymes of the stomach will degrade them.

For use in multiple sclerosis, interferon beta-1a is injected into the muscle (intramuscular injection), and beta-1b is injected just below the skin (subcutaneous injection). The injections are usually given every other day. The recommended dose for beta-1a and 1b is 0.03 mg and 0.25 mg, respectively. Initial doses of beta-1b should be far less (i.e., 0.0625 mg), with a gradual increase in dose over six weeks.

Precautions

Patients who have had seizures or who are at risk for a seizure should be closely monitored following the injection of interferon, as should those with heart disorders such as angina, congestive heart failure, or an irregular heartbeat.

It is not known if interferon can be expressed in breast milk. Concerned mothers may opt to cease breast-feeding while receiving interferon therapy.

Side effects

Interferon beta 1-a and 1-b commonly produce flu-like symptoms, including fever, chills, sweating, muscle aches, and tiredness. These side effects tend to diminish with time. Menstrual cycle changes have also been documented in a significant number of women.

Far less commonly, interferon beta 1-a and 1-b can produce suicidal feelings in someone who is already clinically depressed. Death of cells around an injection site (necrosis) can occur, as can swelling and bruising. Allergic reactions are possible. The massive and sometimes fatal allergic reaction termed anaphylaxis occurs rarely. Other side effects include liver and thyroid malfunction, and altered blood chemistry (fewer platelets and red and white blood cells).

Interactions

As of December 2003, drug interaction studies have not been conducted.

BOOKS

Lotze, M. T., R. M. Dallal, J. M. Kirkwood, and J. C. Flickinger. "Cutaneous Melanoma." In Principles and Practice of Oncology, edited by V. T. DeVita, S. A. Rosenberg, and S. Hellmon. Philadelphia: Lippincott, 2001.

PERIODICALS

Aguilar, R. F. "Interferons in Neurology." Rev Invest Clin 52, no. 6 (2000): 665–679.

Polman, C. H., and B. M. J. Uitdehaag. "Drug Treatment of Multiple Sclerosis." BMJ 321 (2000): 490–494.

OTHER

National Multiple Sclerosis Society. Interferons. National Multiple Sclerosis Society Sourcebook. December 28, 2003. (May 22, 2004). <http://www.nationalmssociety.org/%5Csourcebook-Interferons.asp>.

ORGANIZATIONS

National Multiple Sclerosis Society. 733 Third Avenue, New York, NY 10017. (800) 344-4867. <http://www.nationalmssociety.org>.

Brian Douglas Hoyle, PhD