Obesity impairs Immune Response
Apr 5, 2005 - 5:24:00 PM
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"Another important finding was the reduced ability of natural killer cells in the obese animals. Natural killer cells are another central component of the early immune response. They limit viral replication by killing infected cells and have been shown to be important in the development of the T cell response to influenza."
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By University of North Carolina at Chapel Hill, School of Medicine,
[RxPG] Obesity apparently reduces laboratory mices ability to turn on elements of their immune systems needed for controlling influenza infection, a new University of North Carolina at Chapel Hill School of Medicine study shows.
The findings raise the possibility that obesity in humans has a similar effect, scientists say.
Compared to other mice of normal weight, which were otherwise identical, obese mice were 10 times as likely to die when infected with the flu virus. Four percent of lean mice died during the experiments, compared with 40 percent of the extra fat ones.
Nutrition doctoral student Alexia Smith and Dr. Melinda A. Beck, associate professor of pediatrics at the UNC School of Medicine, led the research and reported the findings.
"Numerous marked alterations seen in the mices immune response suggest that the growing obese population is at increased risk for immune dysfunction during influenza infection, which may lead in humans, as it did in the mice, to increased mortality," Beck said. "Influenza virus currently is responsible for 36,000 deaths and 114,000 hospitalizations in the United States each year."
Mice are a common model in influenza virus infection studies, Beck said. In her UNC laboratory, 35 mice fed a high-fat, high-sugar diet for five months grew 37 percent heavier than 35 mice fed a regular rodent diet high in carbohydrates. The obese mice had a body fat percentage of 31 percent, compared to 21 percent in the lean mice.
"Following influenza infection at five months, which is adulthood for mice, the obese mice demonstrated significantly decreased capacity in every step of the inflammatory immune response in the lungs necessary to stop spread of the virus," Beck said.
The immune response after infection with influenza virus begins with the production of cytokines whose function is to control the spread of infection and turn on various immune system components, she said. This step is followed by activation of T cells that circulate into the lungs to further limit viral spread.
There were considerable differences between the obese and lean animals in both gene expression and protein expression of several antiviral and pro-inflammatory cytokines, the scientist said. Antiviral cytokines, important in the control of initial viral spread, were significantly lower in obese animals. Similarly, some of the pro-inflammatory cytokines, which induce fever, swelling, and recruitment of immune cells, also were significantly lower in obese animals in the early days of infection when they were most needed.
"There were no differences in cytokines important in T cell activation," Beck said. "However, there were differences in chemokine expression, which is important in T cell and monocyte recruitment to the infected tissue."
Monocytes are cells specialized to fight disease organisms by engulfing them.
"Another important finding was the reduced ability of natural killer cells in the obese animals," she said. "Natural killer cells are another central component of the early immune response. They limit viral replication by killing infected cells and have been shown to be important in the development of the T cell response to influenza."
Natural killer cells in the obese animals had a 50 percent reduction in their killing capacity compared to lean animals, Beck said.
Publication:
The study, presented in San Diego Saturday (April 2) at an American Society of Nutritional Sciences scientific meeting, part of a larger experimental biology meeting, is the first of its kind to examine the effects of obesity on the immune response to infection with influenza.
On the web:
www.unc.edu 
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Additional information about the news article
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Co-authors of the paper were medical student Patricia Sheridan and Dr. Joyce Harp, associate professor of nutrition in the schools of medicine and public health.
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