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Interleukin-17: Warrior Cytokine

published:
July 1, 2001
Author:
Shellito, J.E., Zheng, M., Ye, P., Ruan, S., Shean, M.K., & Kolls, J
Citation:

Shellito, J.E., Zheng, M., Ye, P., Ruan, S., Shean, M.K., & Kolls, J. (2001, May). Effect of alcohol consumption on host release of Interleukin-17 during pulmonary infection with Klebsiella pneumoniae. Alcoholism: Clinical and Experimental Research, 25(6), 560-569.

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  • Alcoholics are among those considered most at risk of dying from bacterial pneumonia

  • Alcohol consumption suppresses the release of cytokine Interleukin-17 (IL-17) in response to bacterial infection. In other words, alcohol causes a form of immunosuppression

  • Conversely, gene transfer of IL-17 in an animal model normalizes mortality rates despite continued alcohol consumption

Pneumonia - an inflammation of the lungs caused by an infection - is a very common yet serious illness that affects approximately one out of 100 people in the U.S. each year. In fact, pneumonia and influenza are the fifth leading cause of death in the U.S. Those considered most vulnerable are the elderly, infants and young children, people with medical conditions that damage the immune system, and people who abuse alcohol and/or drugs. A study in the June issue of Alcoholism: Clinical & Experimental Research explains how alcohol abuse can increase an individual’s susceptibility to bacterial pneumonia through suppression of a cytokine called Interleukin-17 (IL-17).

"The body is endowed with a large number of normal defenses," said Judd E. Shellito, Lowenstein professor of medicine at the Louisiana State University Health Sciences Center and lead author of the study. "Every day in the air that you inhale, your lungs are exposed to bacteria, viruses and micro-organisms that can cause pneumonia. The body has a number of host defense mechanisms to fight off these infectious challenges and keep the lungs from developing pneumonia. Research indicates that alcohol can interfere with some of those defense mechanisms, which may explain why alcoholics are more likely than non-alcoholics to get pneumonia. This paper looks at one of those host defense mechanisms, a lymphocyte-derived cytokine called IL-17."

Pneumonia can be caused by bacteria, viruses or fungi. It can be primary or secondary (a complication of another disease), and involve one or both lungs. The microorganisms that give rise to pneumonia are often normal flora in the upper respiratory tract. They cause no damage unless resistance is severely lowered by some other factor, such as smoke and environmental pollutants, drugs and/or alcohol, medical conditions such as AIDS, cancers and chronic bronchitis, and sometimes surgery and certain genetic disorders. The Shellito study found that when bacteria was introduced into the lungs of experimental rodents, IL-17 was released, most likely by lymphocytes (white blood cells formed in lymphatic tissue). Alcohol, however, suppressed the release of IL-17, which led to an increase in mortality from bacterial pneumonia.

"The general public doesn’t tend to fully realize how damaging alcohol is," said Carol Mason, professor of medicine at the Louisiana State University Health Sciences Center. "Alcohol is very destructive in terms of the body’s capability to fight any infection in the lung. Pneumonia is already such a leading cause of death. So, when you put the two together, it portends a potentially bad outcome." As Shellito noted in his study, age-specific death rates due to bacterial pneumonia are three to seven-fold greater among alcoholics than among members of the general population.

"Researchers and medical personnel have long known of the connection between alcoholism and pneumonia," added Mason. "In fact, the bulk of the evidence about alcohol’s detrimental effects on the body is regarding pneumonia. But the exact mechanisms have not been understood. This is a new mechanism."

"This study shows that people who drink have a form of immunosuppression," said Shellito. "This impairment of their immunity is similar to that of people who are HIV infected or take cancer chemotherapeutic drugs. Alcoholism causes a very similar situation to that caused by HIV infection or AIDS, or the way that cancer chemotherapeutic drugs interfere with the immune system and predispose to infection. It’s not as severe, and the actual mechanisms through which it causes that immunosuppression are different, but it causes a similar blunting of the body’s ability to defend itself against infection and mount a strong immune response."

In addition to shedding new light on alcohol’s debilitating effects on the body’s immune system, the study authors also used gene therapy to reintroduce IL-17 into lung tissue while alcohol consumption continued. They found that this procedure normalized mortality rates.

"This finding has important implications for immune system abnormalities among alcoholics," said Shellito. "But first we need to determine what the cellular site of IL-17 release is, where it’s localized, where the cells are that release it, and how they get into the lungs. I’m very interested in whether or not, through immunization or maybe some other approach, we might be able to increase the number of cells that produce IL-17. One way to increase IL-17 in the lungs is to introduce a gene that makes it. Another way is that, if you knew what kind of cell makes it, then you could stimulate the production or the numbers of cells producing IL-17 in the lung tissue, with the same end result."

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