February 27, 2012

Tick, Tock, Disease Ran Up the Clock

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Joseph V. Madia, MD By:

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Circadian rhythms may play a part in how well the immune system fights off disease

(dailyRx News) How sick will you get from exposure to a germ? It may depend on whether it's day or night, based on a new study revealing that human biological clocks may play a part in fighting disease.

Scientists have discovered that the functioning of a key gene in the immune system changes throughout the day.

Its levels at the moment a person is infected, apparently controlled at least partly by circadian rhythms, appears to determine how well the person's body can respond to infection.

"Get enough sleep to avoid getting sick."

Dr. Adam Silver, of the Section of Infectious Diseases in the Department of Internal Medicine at Yale University School of Medicine, led the study, revealing that interruptions in a person's biological clock may affect the severity of an illness.

"People intuitively know that when their sleep patterns are disturbed, they are more likely to get sick," said senior author Erol Fikrig, a professor of epidemiology and microbial pathogenesis at Yale School of Medicine.

"It does appear that disruptions of the circadian clock influence our susceptibility to pathogens," Fikrig said.

Circadian rhythms, or human biological clocks, run a complete cycle of 24 hours and involve the release of certain molecules or hormones in the human body at certain times.

These rhythms regulate human sleeping patterns, periods of alertness, metabolism rates and other biological cycles and processes each day, usually with clues from the environment such as light and darkness.

Meanwhile, the gene called "Toll-like receptor 9" (TLR9) is an important gene in the immune system that reacts to bacteria, viruses and other pathogens that enter the body.

The researchers used mice to test the effectiveness of the immune system when TLR9 was most responsive in the body and then tested whether that responsiveness changed throughout a 24-hour cycle.

When TLR9 was most active, the immune system responded most effectively to vaccination, meaning the mouse had a better immune response to a specific pathogen weeks after the vaccination.

Further, the scientists found that the severity of a disease in a mouse depended on what time of day the mouse was exposed to the infection - which also corresponded to how high or low the functioning of TLR9 was.

If additional studies can determine the times of the day when the immune system is at its peak, this could help people make decisions that would improve their ability to avoid getting sick.

It may be that jet lag from traveling may play a part in getting sick or that getting vaccinations at a certain time of the day may make them more effective.

Previous studies have already shown that children sleep longer when vaccinated in the afternoon, thereby giving them an edge in the effectiveness of the vaccine because of sleep's support of the immune system.

"There are a number of studies out showing the significance of circadian patterns with our immune response," said Dr. William Kohler, director of the Florida Sleep Institute and director of Pediatric Sleep Services at Florida Hospital, Tampa.

"It has applicability not only in looking at when our immune system goes down but also as to when we should give certain drugs to alter immune response," Kohler said. "Certain medications may be more effective if we gave them at the right time based on the circadian clock."

Pinning down the biological clock's peak immune times could also help doctors determine how much and for how long patients should be exposed to light or darkness in the hospital to ensure they recover more quickly and effectively.

"Sleep patterns of patients in intensive care are often disrupted because of the noise and prolonged exposure to artificial light," Fikrig said. "It will be important to investigate how these factors influence immune system response."

The study appeared online February 16 in the journal Immunity. The research was funded by grants from the National Institutes of Health. No conflicts of interest were noted.

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Reviewed by: 
Joseph V. Madia, MD
Review Date: 
February 26, 2012

Last Updated:
July 26, 2012