Microbiology and Immunology

Interferons WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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processes of pregnancy. Although once thought to be a poten-

tial cure-all for a number of viral diseases and cancers, subse-

quent 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 pro-

duce other proteins that prevent virusesfrom replicating. They

named the protein interferon because it interferes with infec-

tion. 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 inter-

ferons, depending on their molecular structure. Two other

classes of interferons, omega and tau, have also been discov-

ered. 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 infec-

tions. Interferon-gamma is the only type II interferon, classi-

fied 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 pro-

duced by almost every cell in the body, while the type II inter-

feron-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 pro-

teins 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 special-

ized 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 fight-

ing disease). Interferon-gamma can also stimulate the produc-

tion of a class of T lymphocytes known as suppressor CD8

cells, which can inhibit B cellsfrom 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 divi-

sion, 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 ther-

apies. 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, pre-

vent 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 dis-

appearance 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 inter-

feron 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 treat-

ing a variety of cancers. Also, biotechnological advances mak-

ing genetic engineering easier and faster are making protein

drugs like interferons more available for study and use. Using

recombinant DNAtechnology, or genesplicing, genes that

code for interferons are identified, cloned, and used for exper-

imental studies and in making therapeutic quantities of pro-

tein. 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 alsoAIDS, recent advances in research and treatment;

Interferon actions; Viral genetics; Viral vectors in gene ther-

apy; Virology; Virus replication; Viruses and responses to

viral infection

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