When interferons were first discovered in the 1950s, it was hoped that these naturally occurring chemicals could do for viruses what penicillin did for bacterial infections. Although that wish didn't quite pan out, interferons have been demonstrating their versatility for years, and they are currently being used to treat different diseases, including multiple sclerosis.
Sidney Pestka, MD, chairman of the Molecular Genetics and Microbiology and Immunology at Robert Wood Johnson Medical School and the Chief Scientific Officer of PBL Biomedical Laboratories and PBL Therapeutics, is sometimes called "the father of interferon." In 2002, he received the National Medal of Technology from President Bush for his pioneering work. Below, he explains how interferon works in different settings and how it might be used more effectively in the future.
What is an interferon?
Interferon is a protein released by many cells in the body in response to various stimuli. There are two classes of interferons. Type I interferons are proteins that are produced in the body in response to a viral infection. In fact, these interferons are an individual's first defense: when the virus reaches other cells, it protects them from infection. When an individual has an infection with influenza virus, the headaches, chills, fever, muscle pain, aches are actually due to the production of interferon. You might say that when you start getting some of these symptoms, you should be grateful because you have something actually attacking the infection. Human interferons that are classified as the Type I are the interferon-alphas, of which there are 12, the interferon-beta and the interferon-omega. The Type II interferon is involved in controlling immune functions in the body and is not produced by viral infection. Interferon-gamma is the only Type II interferon.
How does interferon work in viral diseases?
Interferon prevents cells from infection from many, but not all, viruses. If a cell is treated with interferon, interferon changes the properties of that cell and can prevent the virus from replicating in that cell and leading to the infection of surrounding cells. It does this by a wide variety of mechanisms that vary from virus to virus and from cell to cell. Remarkably, the mechanism also varies from species to species, such as mice and humans, which makes it hard to predict how it will work in humans based on animal studies.
The interferon-alphas are used to treat viral diseases. They're approved by the Food and Drug Administration (FDA) for the treatment of chronic hepatitis B and chronic hepatitis C. They have also been approved for the treatment of papilloma virus infections, which cause genital warts. So those are two of the major viruses that are treated therapeutically with interferon.
Interferon protects cells against the human immunodeficiency virus (HIV), the virus which causes AIDS, in laboratory experiments, but has not been found to be useful in people with HIV or AIDS.
What cancers can interferon treat?
Approximately 180 clinical trials utilize interferon in cancer today. Interferon alpha is the predominant interferon in cancer today.
Interferon has been approved for the treatment of advanced malignant melanoma. At high doses, it was found in clinical trials to increase the survival of patients with this cancer. Additionally, interferon is the major therapy for Kaposi sarcoma, a cancer of the skin that occurs in patients with AIDS. Interferon was an early treatment for chronic myelogenous leukemia, but now Gleevec has been found to be effective in that disease, so interferon has been used less often. Another cancer in which it was quite effective is called hairy cell leukemia, which is a rare type of leukemia with cells that look like they have a hairy surface.
How is interferon effective in treating cancers?
In cancer, interferon works in quite a different way than it does in viruses. And there are numerous pathways that interferon activates to help treat cancers.
Interferon has an antiproliferative effect on tumor cells, that is, it inhibits their growth directly. At the same time, the interferon stimulates the tumor cells to change their surfaces so that they are recognized by the immune system as abnormal cells. The modified tumor cells can then be seen by the immune system and attacked. In the process, interferon activates immune system cells to kill the tumor cells.
Also, in order for tumors to grow, they need a continuous supply of nutrients. To do this, they produce new blood vessels—a process called angiogenesis—that provide nutrients. Interferon blocks the growth of new blood vessels and helps cut off the supply of nutrients.
How does interferon affect MS?
It has been clearly shown that there is efficacy with interferon-beta in the relapsing remitting type of the MS. In the presence of interferon, the time where MS remains in remission increases, whereas the time when it relapses decreases. No one knows specifically why it's working in MS.
Are type II interferons ever used in treatment?
Interferon-gamma is approved for the treatment of a rare lung disease called chronic granulomatous disease.
What are some side effects experienced during interferon therapy?
Common side effects include headache, chills, fever, back pain, joint pain and anorexia. At high-dose levels of interferon, the side effects become debilitating to the patients. In general, the side effects of interferon are reversible, so when the patient stops taking interferon, the symptoms disappear.
Interferon could be more effective in the treatment of disease, but the side effects limit the dosage. Currently, interferon is provided by injecting it into the arm or leg, and it is distributed all over the body from there. In order to get a significant amount of interferon to the tumor, you need to inject a large amount of interferon into the body. Often, a patient cannot tolerate the quantity that would be required to eliminate tumors.
What about the future of interferon?
My belief is that interferon is going to be effective in treating most solid tumors if a sustained-release system can keep interferon in the tumor. If it were possible to keep the interferon in the tumors and not have lots of it floating around elsewhere, I believe the interferon would be much more effective.
I think it's also going to be a main therapy for many other viral diseases. For example, interferon has been proven to be able to prevent approximately 50 percent of common colds, but it is not currently used for colds for a wide variety of reasons. Another virus that causes the common cold that you've heard a lot about lately is a coronavirus called the SARS (Severe Acute Respiratory Syndrome) virus. And that virus, I believe, could potentially be prevented or treated by interferon. The National Institute of Allergy and Infectious Disease is now working with our laboratory, and coordinating efforts with the Centers for Disease Control and Prevention as well as the Department of Defense, to test our new interferons against the SARS virus. I certainly hope they work. Interferons do have some efficacy against coronaviruses, but we won't know until they have all been tested whether they're going to be effective against this coronavirus.
