PULLMAN – The finding was a paradox. In a study involving malignant melanoma, it was discovered that increased alcohol consumption resulted in decreased spread of the cancer into the lungs of mice. (Gary Medows, left and Hui Zhang, Photo by Becky Philips, WSU Today)
Researcher Gary Meadows expected the mice to live longer as a result, but they didn’t.
Last fall, Meadows was awarded a five-year, $1 million grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in part to try to explain the mechanism behind this paradoxical discovery. As Dorothy O. Kennedy Distinguished Professor in the College of Pharmacy and director of WSU’s Chronic Illness Research Center (formerly the Cancer Prevention and Research Center; see ONLINE @ www.chronicillness.wsu.edu), Meadows also was being honored for his life-long career as a scientist and mentor to young investigators.
Meadows is among a handful of researchers who study the biomedical interplay between cancer and alcohol. For more than a decade he has doggedly pursued the rationale underlying the melanoma case, while coincidentally providing new insight on the role of the immune system in promoting or suppressing tumors. His work also offers hope for developing new therapies to treat immunologic deficiencies in alcoholics.
Alcohol suppresses immunity
It’s no secret to medical practitioners that alcohol abuse wreaks havoc on the body’s immune system. High alcohol intake is immunosuppressive and can heighten susceptibility to viral, bacterial and fungal diseases. Alcoholics are more likely to get bacterial pneumonia and twice as likely to die from it as are nonalcoholics.
Alcoholism also raises the level of autoimmune antibodies in the blood and has been implicated in a number of cancers such as head, neck, lung, esophageal, pancreas and liver. Even low amounts of alcohol appear to increase the risk factor for breast cancer in women.
Although many researchers are investigating alcohol’s role in infectious disease, fewer are studying the relationship between alcohol and cancer.
“There is very little published about the affect alcohol has on the growth and spread of cancer once you already have it,” said Meadows. “Does it increase growth? Decrease growth? Affect the spread throughout the body? Does it affect survival?”
Hoping to answer those questions, Meadows and Hui Zhang, research assistant professor in the department of pharmaceutical sciences, are probing the complex processes of long-term, high-level alcohol use. With the NIAAA grant they also hope to explore the effects of low and moderate levels of alcohol on melanoma and other types of cancer.
“We know that one or two glasses of wine don’t suppress the immune response,” said Meadows. “However, we don’t know how they affect cancer metastasis or growth.”
Other studies in the field have suggested that binge drinking may enhance metastasis.
Other studies in the field have suggested that binge drinking may enhance metastasis.
Natural killer cells
The immune system is composed of an infantry of white blood cells that guard the body against disease, debris and aberrant “mutant cells.” B- and T-lymphocytes are well-known players in this system, but another type of lymphocyte — the natural killer cell (NK) — is important for removing mutant cells in the early stages of cancer.
The immune system is composed of an infantry of white blood cells that guard the body against disease, debris and aberrant “mutant cells.” B- and T-lymphocytes are well-known players in this system, but another type of lymphocyte — the natural killer cell (NK) — is important for removing mutant cells in the early stages of cancer.
NK cells also produce cytokines — small proteins that play a role in immunity, inflammation and the production of blood cells.
In research trials following the original melanoma study, Meadows and Zhang were among the first to validate how heavy alcohol use disables this front-line immune defense. They found that chronic alcohol consumption decreases the number of NK cells and T-lymphocytes in the body — mainly through destruction in the spleen. Additionally, alcoholism is known to shut down the production of a key cytokine called IL-15.
Cytokines to the rescue
Continuing their scientific sleuthing, Meadows and Zhang recently completed a study showing that the destruction of NK cells in the spleen can be reversed. By treating mice with cytokines — IL-15 in combination with IL-15 receptor alpha — they were able to reduce NK cell death in the spleen while simultaneously increasing cell numbers in circulation. The treatment worked even for control mice that drank only water.
Continuing their scientific sleuthing, Meadows and Zhang recently completed a study showing that the destruction of NK cells in the spleen can be reversed. By treating mice with cytokines — IL-15 in combination with IL-15 receptor alpha — they were able to reduce NK cell death in the spleen while simultaneously increasing cell numbers in circulation. The treatment worked even for control mice that drank only water.
In the future, Meadows believes that IL-15 could be a promising new treatment to help correct immune dysfunction in chronic alcoholics. It may also be an emerging therapy for controlling the growth and metastasis of melanoma and other tumors.
“We are very excited about these possibilities and continuing our research,” said Meadows. “Melanoma has been a kind of model for developing immunological approaches to the treatment of cancer. It is one of the few tumors where treatments, such as vaccines, are being developed.”
For more information, see ONLINE @ www.pharmacy.wsu.edu/PharmSci/meadows.html.
