Interferons

Interferons are species-specific proteins that induce antiviral and antiproliferative responses in animal cells. They are a major defense against viral infections and abnormal growths (neoplasms). Interferons are produced in response to penetration of animal cells by viral (or synthetic) nucleic acid and then leave the infected cell to confer resistance on other cells of the organism .

Interferons are a group of proteins known primarily for their role in inhibiting viral infections and in stimulating the entire immune system to fight disease . Research has also shown that these proteins play numerous roles in regulating many kinds of cell functions. They can promote or hinder the ability of some cells to differentiate, that is, to become specialized in their function. They can inhibit cell division , which is one reason why they hold promise for stopping cancer growth. Recent studies have also found that one interferon may play an important role in the early biological processes of pregnancy. Although once thought to be a potential cure-all for a number of viral diseases and cancers, subsequent research has shown that interferons are much more limited in their potential. Still, several interferon proteins have been approved as therapies for diseases like chronic hepatitis , genital warts, multiple sclerosis, and several cancers.

The first interferon was discovered in 1957 by Alick Isaacs and Jean Lindenmann. During their investigation, the two scientists found that virus-infected cells secrete a special protein that causes both infected and noninfected cells to produce other proteins that prevent viruses from replicating. They named the protein interferon because it "interferes" with infection . Initially, scientists thought there was only one interferon protein, but subsequent research showed that there are many different interferon proteins.

Types of interferons and how they work

Interferons are members of a larger class of proteins called cytokines (proteins that carry signals between cells). Most interferons are classified as alpha, beta, or gamma interferons, depending on their molecular structure. Two other classes of interferons—omega and tau—have also been discovered. So far, more than 20 different kinds of interferon-alpha have been discovered but only beta and one gamma interferon have been identified.

Interferons are differentiated primarily through their amino acid sequence. (Amino acids are molecular chains that make up proteins.) Interferon-alpha, -beta, -tau, and -omega, which have relatively similar amino acid sequences, are classified as type I interferons. Type I interferons are known primarily for their ability to make cells resistant to viral infections. Interferongamma is the only type II interferon, classified as such because of its unique amino acid sequence. This interferon is known for its ability to regulate overall immune system functioning.

In addition to their structural makeup, type I and type II interferons have other differences. Type I interferons are produced by almost every cell in the body while the type II interferon-gamma is produced only by specialized cells in the immune system known as T lymphocytes and natural killer cells. The two classes also bind to different kinds of receptors, which lie on the surface of cells and attract and combine with specific molecules of various substances.

Interferons work to stop a disease when they are released into the blood stream and then bind to cell receptors. After binding, they are drawn inside the cell's cytoplasm, where they cause a series of reactions that produce other proteins that fight off disease. Scientists have identified over 30 disease fighting proteins produced by interferons.

In contrast to antibodies, interferons are not virus specific but host specific. Thus, viral infections of human cells are inhibited only by human interferon. The human genome contains 14 nonallelic and 9 allelic genes of alpha-interferon (macrophage interferon), as well as a single gene for beta-interferon (fibroblast interferon). Genes for any two or more variants of interferon, which have originated from the same wild-type gene are called allelic genes and will occupy the same chromosomal location (locus ). Variants originating from different standard genes are termed non allelic. Alpha- and beta-interferons are structurally related glycoproteins of 166 and 169 amino acid residues. In contrast, gamma-interferon (also known as immune interferon) is not closely related to the other two and is not induced by virus infection. It is produced by T cells after stimulation with the cytokine interleukin-2. It enhances the cytotoxic activity of T cells, macrophages and natural killer cells and thus has antiproliferative effects. It also increases the production of antibodies in response to antigens administered simultaneously with alpha-interferon, possible by enhancing the antigen-presenting function of macrophages.

Interferons bind to specific receptors on the cell surface, and induce a signal in the cell interior. Two induction mechanisms have been elucidated. One mechanism involves the induction of protein kinase by interferon, which, in the presence of double-stranded RNA, phosphorylates one subunit of an initiation factor of protein synthesis (eIF-2B), causing the factor to be inactivated by sequestration in a complex. The second mechanism involves the induction of the enzyme 2',5'-oligoadenylate synthetase (2',5'-oligo A synthestase). In the presence of double-stranded RNA, this enzyme catalyses the polymerisation of ATP into oligomers of 2 to 15 adenosine monophosphate residues which are linked by phosphodiester bonds between the position 2' of one ribose and 5' of the next. These 2',5'-oligoadenylates activate an interferon specific RNAase, a latent endonuclease known as RNAase L which is always present but not normally active. RNAase cleaves both viral and cellular single stranded mRNA. Interferons therefore do not directly protect cells against viral infection, but rather render cells less suitable as an environment for viral replication. This condition is known as the antiviral state.

Interferons and the immune system

In addition to altering a cell's ability to fight off viruses, interferons also control the activities of a number of specialized cells within the immune system. For example, type I interferons can either inhibit or induce the production of B lymphocytes (white blood cells that make antibodies for fighting disease). Interferon-gamma can also stimulate the production of a class of T lymphocytes known as suppressor CD8 cells, which can inhibit B cells from making antibodies.

Another role of interferon-gamma is to increase immune system functioning by helping macrophages, still another kind of white blood cell, to function. These scavenger cells attack infected cells and also stimulate other cells within the immune system. Interferon-gamma is especially effective in switching on macrophages to kill tumor cells and cells that have been infected by viruses, bacteria , and parasites .

Interferon-tau, first discovered for its role in helping pregnancy to progress in cows, sheep , and goats , also has antiviral qualities. It has been shown to block tumor cell division and may interfere with the replication of the acquired immune deficiency, or AIDS , virus. Since it has fewer unwanted side-effects (flu-like symptoms and decreased blood cell production) than the other interferons, interferon-tau is becoming a new focal point for research.

Interferon's medical applications

In 1986, interferon-alpha became the first interferon to be approved by the Food and Drug Administration (FDA) as a viable therapy, in this case, for hairy-cell leukemia . (Interferons are used therapeutically by injecting them into the blood stream.) In 1988, this class of interferons was also approved for the treatment of genital warts, proving effective in nearly 70% of patients who do not respond to standard therapies. In that same year, it was approved for treatment of Kaposi's sarcoma, a form of cancer that appears frequently in patients suffering from AIDS. In 1991, interferon-alpha was approved for use in chronic hepatitis C, a contagious disease for which there was no reliable therapy. Interferon has been shown to eliminate the disease's symptoms and, perhaps, prevent relapse. Interferon-alpha is also used to treat Hodgkin's lymphoma and malignant melanoma, or skin cancer.

In 1993, another class of interferon, interferon-gamma, received FDA approval for the treatment of a form of multiple sclerosis characterized by the intermittent appearance and disappearance of symptoms. It has also been used to treat chronic granulomatous diseases, an inherited immune disorder in which white blood cells fail to kill bacterial infections, thus causing severe infections in the skin, liver, lungs, and bone. Interferon-gamma may also have therapeutic value in the treatment of leishmaniasis, a parasitic infection that is prevalent in parts of Africa , America, Europe , and Asia .

Although all of the disease fighting attributes of interferon demonstrated in the laboratory have not been attained in practice, continued research into interferons will continue to expand their medical applications. For example, all three major classes of interferons are under investigation for treating a variety of cancers. Also, biotechnological advances making genetic engineering easier and faster are making protein drugs like interferons more available for study and use. Using recombinant DNA technology, or gene splicing , genes that code for ineterferons are identified, cloned, and used for experimental studies and in making therapeutic quantities of protein. These modern DNA manipulation techniques have made possible the use of cell-signaling molecules like interferons as medicines. Earlier, available quantities of these molecules were too minute for practical use.

Another particular area of interest is the use of inter-ferons to enhance other therapies. For example, studies have shown that a combination of interferon-alpha and tamoxifen may be a more effective therapy for breast cancer than either used alone. Future studies will focus more on combining interferons with other drug therapies.

See also Antibody and antigen; Immunology.

Resources

books

Janeway, Charles A., et al. Immunobiology. 5th ed. New York and London: Garland Publishing, 2001.

periodicals

Johnson, Howard M., Fuller W. Bazer, Brian E. Szente, and Michael A. Jarpe. "How Interferons Fight Disease." Scientific American (May 1994): 68–76.

Meulen, Volkerter, and Stefan Niewiesk. "Inhibition of Major Histocompatibility Complex Class II-Dependant Antigen Presentation by Nutralization of Gamma Interferon Leads to Breakdown of Resistance against Measles Virus-Induced Encephalitis." Journal of Virology 75 (2000):1–13.

Seppa, Nathan. "Interferon Delays Multiple Sclerosis." ScienceNews 158 (November 2000): 280–281.

other

Multiple Sclerosis Society. Interferons. [cited April 3, 2003] <http://www.interferons.com>.

Worman, M.D., J. Howard. "Interferon Treatment of Viral He patitis". Dept. of Gastrointestinal Diseases, Columbia University. April 6, 2002 [January 2003]. <http://cpmcnet.coumbia.edu/dept/gi/intron.html>.

David Petechuk Judyth Sassoon

KEY TERMS

Immune system

—That network of tissues and cells throughout the body which is responsible for ridding the body of invaders such as viruses, bacteria, protozoa, etc.

Proteins

—Macromolecules made up of long sequences of amino acids. They make up the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other essential life functions.

Type I interferons

—A group of interferons that have similar amino acid sequences. They include the alpha, beta, tau, and omega interferons.

Type II interferons

—A type of interferon that has a unique amino acid sequence. Interferon gamma is the only interferon in this group.

Interferons

Resources

Interferon is the name given to a group of proteins known primarily for their role in inhibiting viral infections and in stimulating the entire immune system to fight disease. Research has also shown that these proteins play numerous roles in regulating many kinds of cell functions. Interferons can promote or hinder the ability of some cells to differentiate, that is, to become specialized in their function. They can inhibit cell division, which is one reason why they hold promise for stopping cancer growth. Recent studies have also found that one interferon may play an important role in the early biological processes of pregnancy. Although once thought to be a potential cure-all for a number of viral diseases and cancers, subsequent research has shown that interferons are much more limited in their potential. Still, several interferon proteins have been approved as therapies for diseases like chronic hepatitis, genital warts, multiple sclerosis, and several cancers.

The first interferon was discovered in 1957 by Alick Isaacs and Jean Lindenmann. During their investigation, the two scientists found that virus-infected cells secrete a special protein that causes both infected and noninfected cells to produce other proteins that prevent viruses from replicating. They named the protein interferon because it interferes with infection. Initially, scientists thought there was only one interferon protein, but subsequent research showed that there are many different interferon proteins.

Interferons are members of a larger class of proteins called cytokines (proteins that carry signals between cells). Most interferons are classified as alpha, beta, or gamma interferons, depending on their molecular structure. Two other classes of interferons, omega and tau, have also been discovered. So far, more than 20 different kinds of interferon-alpha have been discovered but few beta and gamma interferons have been identified.

Interferons are differentiated primarily through their amino acid sequence. (Amino acids are molecular chains that make up proteins.) Interferon-alpha, -beta, -tau, and -omega, which all have relatively similar amino acid sequences, are classified as type I interferons. Type I interferons are known primarily for their ability to make cells resistant to viral infections. Interferon-gamma is the only type II interferon, classified as such because of its unique amino acid sequence. This interferon is known for its ability to regulate overall immune system functioning.

In addition to their structural makeup, type I and type II interferons have other differences. Type I interferons are produced by almost every cell in the body, while the type II interferon-gamma is produced only by specialized cells in the immune system known as T lymphocytes and natural killer cells. The two classes also bind to different kinds of receptors, which lie on the surface of cells, and attract and combine with specific molecules of various substances.

Interferons work to stop a disease when they are released into the blood stream and then bind to cell

receptors. After binding, they are drawn inside the cell’s cytoplasm, where they cause a series of reactions that produce other proteins that fight off disease. Scientists have identified over 30 disease-fighting proteins produced by interferons.

In addition to altering a cell’s ability to fight off viruses, interferons also control the activities of a number of specialized cells within the immune system. For example, type I interferons can either inhibit or induce the production of B lymphocytes (white blood cells that make antibodies for fighting disease). Interferon-gamma can also stimulate the production of a class of T lymphocytes known as suppressor CD8 cells, which can inhibit B cells from making antibodies.

Another role of interferon-gamma is to increase immune system functioning by helping macrophages, still another kind of white blood cell, to function. These scavenger cells attack infected cells while also stimulating other cells within the immune system. Interferon-gamma is especially effective in switching on macrophages to kill tumor cells and cells that have been infected by viruses, bacteria, and parasites.

Interferon-tau, first discovered for its role in helping pregnancy to progress in cows, sheep, and goats, also has antiviral qualities. It has been shown to block tumor cell division, and may interfere with the replication of the acquired immune deficiency, or AIDS, virus. Because it has fewer unwanted side-effects (flulike symptoms and decreased blood cell production) than the other interferons, interferon-tau is becoming a new focal point for research.

In 1986, interferon-alpha became the first interferon to be approved by the Food and Drug Administration (FDA) as a viable therapy, in this case, for hairy-cell leukemia. (Interferons are used therapeutically by injecting them into the blood stream.) In 1988, this class of interferons was also approved for the treatment of genital warts, proving effective in nearly 70% of patients who do not respond to standard therapies. In that same year, it was approved for treatment of Kaposi’s Sarcoma, a form of cancer that appears frequently in patients suffering from AIDS. In 1991, interferon-alpha was approved for use in chronic hepatitis C, a contagious disease for which there was no reliable therapy. Interferon has been shown to eliminate the disease’s symptoms and, perhaps, prevent relapse. Interferonalpha is also used to treat Hodgkin’s lymphoma and malignant melanoma.

KEY TERMS

Immune system —That network of tissues and cells throughout the body which is responsible for ridding the body of invaders such as viruses, bacteria, protozoa, etc.

Proteins —Macromolecules made up of long sequences of amino acids. They make up the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other essential life functions.

Type I interferons —A group of interferons that have similar amino acid sequences. They include the alpha, beta, tau, and omega interferons.

Type II interferons —A type of interferon that has a unique amino acid sequence. Interferon gamma is the only interferon in this group.

In 1993, another class of interferon, interferon-gamma, received FDA approval for the treatment of a form of multiple sclerosis characterized by the intermittent appearance and disappearance of symptoms. It has also been used to treat chronic granulomatous diseases, inherited immune disorders in which white blood cells fail to kill bacterial infections, thus causing severe infections in the skin, liver, lungs, and bone. Interferon-gamma may also have therapeutic value in the treatment of leishmaniasis, a parasitic infection that is prevalent in parts of Africa, America, Europe, and Asia.

Although all of the disease fighting attributes of interferon demonstrated in the laboratory have not been attained in practice, continued research into interferons will continue to expand their medical applications. For example, all three major classes of interferons are under investigation for treating a variety of cancers. Also, biotechnological advances making genetic engineering easier and faster are making protein drugs like interferons more available for study and use. Using recombinant DNA technology, or gene splicing, genes that code for interferons are identified, cloned, and used for experimental studies and in making therapeutic quantities of protein. These modern DNA manipulation techniques have made possible the use of cell-signaling molecules like interferons as medicines. Earlier, available quantities of these molecules were too minute for practical use.

Resources

BOOKS

Burns, Cameron. Hep is on the Way: A Comprehensive Guide to Hepatitis C and Interferon Treatment. Bloomington: Authorhouse, 2005.

Meager, Anthony. The Interferons: Characterization and Application. New York: John Wiley & Sons, 2006.

Pieters, Toine. Interferon: The Science and Selling of a Miracle Drug. Oxford: Routledge, 2005.

OTHER

Multiple Sclerosis Society. Interferons. Multiple Sclerosis Society. Apr. 03, 2002. <http://www.interferons.com> (accessed October 31, 2006).

David Petechuk
Judyth Sassoon

Interferons

Interferon is the name given to a group of proteins known primarily for their role in inhibiting viral infections and in stimulating the entire immune system to fight disease. Research has also shown that these proteins play numerous roles in regulating many kinds of cell functions. Interferons can promote or hinder the ability of some cells to differentiate, that is, to become specialized in their function. They can inhibit cell division, which is one reason why they hold promise for stopping cancer growth. Recent studies have also found that one interferon may play an important role in the early biological processes of pregnancy. Although once thought to be a potential cure-all for a number of viral diseases and cancers, subsequent research has shown that interferons are much more limited in their potential. Still, several interferon proteins have been approved as therapies for diseases like chronic hepatitis , genital warts, multiple sclerosis, and several cancers.

The first interferon was discovered in 1957 by Alick Isaacs and Jean Lindenmann. During their investigation, the two scientists found that virus-infected cells secrete a special protein that causes both infected and noninfected cells to produce other proteins that prevent viruses from replicating. They named the protein interferon because it interferes with infection. Initially, scientists thought there was only one interferon protein, but subsequent research showed that there are many different interferon proteins.

Interferons are members of a larger class of proteins called cytokines (proteins that carry signals between cells). Most interferons are classified as alpha, beta, or gamma interferons, depending on their molecular structure. Two other classes of interferons, omega and tau, have also been discovered. So far, more than 20 different kinds of interferon-alpha have been discovered but few beta and gamma interferons have been identified.

Interferons are differentiated primarily through their amino acid sequence. (Amino acids are molecular chains that make up proteins.) Interferon-alpha, -beta, -tau, and -omega, which all have relatively similar amino acid sequences, are classified as type I interferons. Type I interferons are known primarily for their ability to make cells resistant to viral infections. Interferon-gamma is the only type II interferon, classified as such because of its unique amino acid sequence. This interferon is known for its ability to regulate overall immune system functioning.

In addition to their structural makeup, type I and type II interferons have other differences. Type I interferons are produced by almost every cell in the body, while the type II interferon-gamma is produced only by specialized cells in the immune system known as T lymphocytes and natural killer cells. The two classes also bind to different kinds of receptors, which lie on the surface of cells, and attract and combine with specific molecules of various substances.

Interferons work to stop a disease when they are released into the blood stream and then bind to cell receptors. After binding, they are drawn inside the cell's cytoplasm , where they cause a series of reactions that produce other proteins that fight off disease. Scientists have identified over 30 disease-fighting proteins produced by interferons.

In addition to altering a cell's ability to fight off viruses, interferons also control the activities of a number of specialized cells within the immune system. For example, type I interferons can either inhibit or induce the production of B lymphocytes (white blood cells that make antibodies for fighting disease). Interferon-gamma can also stimulate the production of a class of T lymphocytes known as suppressor CD8 cells, which can inhibit B cells from making antibodies.

Another role of interferon-gamma is to increase immune system functioning by helping macrophages, still another kind of white blood cell, to function. These scavenger cells attack infected cells while also stimulating other cells within the immune system. Interferon-gamma is especially effective in switching on macrophages to kill tumor cells and cells that have been infected by viruses, bacteria , and parasites .

Interferon-tau, first discovered for its role in helping pregnancy to progress in cows, sheep, and goats, also has antiviral qualities. It has been shown to block tumor cell division, and may interfere with the replication of the acquired immune deficiency, or AIDS , virus. Because it has fewer unwanted side-effects (flu-like symptoms and decreased blood cell production) than the other interferons, interferon-tau is becoming a new focal point for research.

In 1986, interferon-alpha became the first interferon to be approved by the Food and Drug Administration (FDA) as a viable therapy, in this case, for hairy-cell leukemia. (Interferons are used therapeutically by injecting them into the blood stream.) In 1988, this class of interferons was also approved for the treatment of genital warts, proving effective in nearly 70% of patients who do not respond to standard therapies. In that same year, it was approved for treatment of Kaposi's Sarcoma, a form of cancer that appears frequently in patients suffering from AIDS. In 1991, interferon-alpha was approved for use in chronic hepatitis C, a contagious disease for which there was no reliable therapy. Interferon has been shown to eliminate the disease's symptoms and, perhaps, prevent relapse. Interferon-alpha is also used to treat Hodgkin's lymphoma and malignant melanoma.

In 1993, another class of interferon, interferon-gamma, received FDA approval for the treatment of a form of multiple sclerosis characterized by the intermittent appearance and disappearance of symptoms. It has also been used to treat chronic granulomatous diseases, inherited immune disorders in which white blood cells fail to kill bacterial infections, thus causing severe infections in the skin, liver, lungs, and bone. Interferon-gamma may also have therapeutic value in the treatment of leishmaniasis, a parasitic infection that is prevalent in parts of Africa, America, Europe, and Asia.

Although all of the disease fighting attributes of interferon demonstrated in the laboratory have not been attained in practice, continued research into interferons will continue to expand their medical applications. For example, all three major classes of interferons are under investigation for treating a variety of cancers. Also, biotechnological advances making genetic engineering easier and faster are making protein drugs like interferons more available for study and use. Using recombinant DNA technology, or gene splicing, genes that code for interferons are identified, cloned, and used for experimental studies and in making therapeutic quantities of protein. These modern DNA manipulation techniques have made possible the use of cell-signaling molecules like interferons as medicines. Earlier, available quantities of these molecules were too minute for practical use.

See also AIDS, recent advances in research and treatment; Interferon actions; Viral genetics; Viral vectors in gene therapy; Virology; Virus replication; Viruses and responses to viral infection

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.

Resources

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

Interferons

Definition

Interferons are small, natural or synthetic protein and glycoprotein cytokines that are produced by leucocytes, T-lymphocytes, and fibroblasts in response to infection and other biological stimuli. In cancer treatment, they are used as immunotherapy against the proliferation of cancer cells.

Purpose

The goal of interferon use is to activate tumor-specific cytotoxic T-lymphocytes. T-lymphocytes are cells of the immune system that destroy foreign cells. Thus, tumor cells would be destroyed based on immunotherapy.

Description

Interferons attach to special receptors on the surface of cell membranes. They have a variety of functions, including enhancing or inhibiting enzymes, decreasing cell proliferation, or enhancing the activity of macrophages and T-lymphocytes. There are several different classes of interferons, including alpha, beta, gamma, tau, and omega. The classes can be further broken into subclasses and classified using Arabic numerals and letters. Cancer therapy research primarily focuses on alpha interferons.

In 1957 researchers discovered that the immune system produced a substance in response to a viral infection that acted as an anti-viral agent. They called that substance "interferon." Since then, recombinant DNA technology has provided a larger supply of interferons and has allowed extensive research regarding interferon's therapeutic properties against cancer.

Alpha interferons are used to treat cancers such as hairy cell leukemia , malignant melanoma , and Kaposi's sarcoma (an AIDS-related cancer). Off the label, alpha interferons are used to treat many other cancers including bladder cancer , chronic myelocytic leukemia , kidney cancer, carcinoid tumors, non-Hodgkin's lymphomas , ovarian cancer , and skin cancers. Alpha interferons can be combined with other chemotherapeutic drugs such as doxorubicin .

In the United States alpha interferons are sold under the brand names Roferon-A (Interferon Alfa-2a, recombinant) and Intron A (Interferon Alfa-2b, recombinant). There are no generic forms of these drugs.

Recommended dosage

Alpha interferons are only available by prescription and are given parenterally. A physician will determine dosage based on several factors such as what type of cancer is being treated, the patient's weight, and what other types of medications the patient is taking. Therefore, the dose will vary from patient to patient.

Patients can inject this drug themselves. Their physician may recommend that they drink extra water to avoid low blood pressure while on this medication. Since this drug can have flu-like side effects, it is recommended that patients inject the drug prior to bedtime so that they are sleeping during the worst part of the side effects.

Precautions

Alpha interferons have not been shown to cause problems in the fetus of pregnant women. Because it is not known whether this drug can cross over into breast milk, it is not recommended for use in women who are breast-feeding. Before this drug is given, patients should notify their doctors if they are allergic to immunoglobulins or egg whites.

There are several medical conditions that should be considered prior to deciding whether to use alpha interferons. There can be an increase in the following disorders: bleeding problems, mental problems, convulsions, diabetes mellitus, heart attack, heart disease, liver disease, kidney disease, and lung disease. People with an overactive immune system could also have this disorder exacerbated when using alpha interferons.

Caution should be taken when using alpha interferons because they can depress the number of white blood cells. This can make patients more susceptible to infection. Therefore, they should avoid contact with others who have infections and should contact their physician immediately if they think they are developing an infection. Patients should take care not to cut themselves, should not touch their eyes or inside of their nose with unwashed hands, and should take care when brushing their teeth so as not to cause bleeding.

The effects of alcohol can be exaggerated while taking alpha interferons. Alcohol should only be used by permission from a physician.

Side effects

Alpha interferons can have side effects that range from minor and irritating to major and severe, needing immediate attention. Some of the less serious side effects are muscle aches, unusual metallic taste in the mouth, fever and chills, and general flu-like symptoms such as headache, loss of appetite (anorexia ), nausea and vomiting , and fatigue . To reduce the flu-like symptoms physicians may suggest that the patient take acetaminophen (e.g., Tylenol) before each dosage.

Other side effects may need medical attention. Any changes with the central nervous system such as confusion, trouble thinking and focusing, mental depression , nervousness, or numbness or tingling of fingers, toes and face require immediate medical attention.

The side effects are dependent on the dose. As a result, the physician may modify the dose if the side effects are severe.

Interactions

Alpha interferons can interact with several different drugs, increasing their effects. Most drugs that interact with alpha interferons are those used with disorders of the central nervous system. Some of the depressants include antihistamines, sedatives, tranquilizers, sleeping medications, prescription pain medicines, seizure medications, muscle relaxants, narcotics, and barbiturates. Prior to treatment, the doctor should be notified if the patient is taking any of these medications because this could impact the dosage prescribed.

Sally C. McFarlane-Parrott

KEY TERMS

Cytokines

—Molecules released by cells to regulate the length and intensity of an immune response and to mediate intercellular communication.

Glycoprotein

—A protein that has a carbohydrate group attached.

Immunotherapy

—Treating cancer using molecules that are intended to stimulate the patient's own immune system to fight the disease.

Macrophages

—A type of white blood cell that produces antibodies and molecules for cell-to-cell immune responses.

Parenteral

—Medications that are administered by some means other than through the gastrointestinal tract, including through intravenous, subcutaneous, or intramuscular injection.

T-lymphocytes

—A part of the immune system that fights foreign cells.