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.
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