Postdoctoral researcher Brian Prendergast says the study suggests hibernating mammals wake regularly to do a "system check." Inset: A golden-mantled ground squirrel.     By Jo McCulty

Immune system turned off during hibernation in squirrels

The immune system of ground squirrels essentially shuts down when the animals go into hibernation each winter, according to a new study.

When scientists injected hibernating squirrels with a pseudo-bacteria that would normally provoke an immune response, they were surprised by what they found: The squirrels didn't react at all.

But when the squirrels aroused briefly from hibernation days later -- as they do normally about once a week during winter -- the squirrels spiked a fever as if they had just been infected.

The results offer one clue as to why all mammals that hibernate arouse at regular intervals during the winter, said Brian Prendergast, co-author of the study and a post-doctoral researcher in psychology at Ohio State.

"Animals may arouse from hibernation to do a'system check' for infections and parasites that they have picked up," Prendergast said. "If they didn't wake up occasionally and activate their immune system, they may not survive until spring."

Prendergast conducted the study with Randy Nelson, professor of psychology and neuroscience at Ohio State, and David Freeman and Irving Zucker of the University of California, Berkeley. The results were published in the April 2002 issue of the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology.

The researchers studied 31 golden-mantled ground squirrels, a native of California, in a laboratory. These squirrels normally spend five to six months each year in hibernation, during which time their core body temperature drops to 1-2 degrees Celsius above the air temperature around them. Normally, the squirrels arouse from hibernation about once a week for 12 to 20 hours at a time and then return to hibernation.

In this study, the squirrels were implanted with radio transmitters that sent the researchers updates on the animals' body temperature. When the squirrels went into hibernation in the lab, the researchers injected some squirrels with lipopolysaccharide (LPS) -- the dead, outer cell wall of bacteria that stimulates an immune reaction. The scientists were surprised to find that the squirrels generally exhibited no immune reaction to the LPS -- most did not come out of hibernation and they did not show a fever.

Photo by Mark Chappell, Stanford University

However, several days later when the squirrels had their normal arousal from hibernation, the infected animals' temperature "skyrocketed into a fever as if they had just been injected with the bacteria," Prendergast said. They averaged a fever of 1 to 1.5 degrees Celsius, comparable to control squirrels who were not hibernating when they were injected with LPS.

"The immune system of these animals didn't seem to recognize a bacterial infection during a hibernation bout. But when they came out of hibernation, the immune system reacted strongly," he said.

In order to learn more about what was happening, the researchers did another experiment in which they infused the hormone prostaglandin E2 into the brains of some hibernating squirrels after they were injected with the LPS. Prostaglandin is the hormone that tells the brain to spike a fever when the animal picks up an infection.

Squirrels that were infused with the prostaglandin immediately came out of hibernation and spiked a fever. "This shows the fever mechanism still works in the hibernating squirrels," Nelson said. "However, the animal's immune system does not activate a fever during hibernation."

Nelson said researchers are unsure why the immune system doesn't function normally during hibernation; however, he noted that most of the body's major systems are shut off or substantially reduced while an animal is hibernating.

Prendergast said the squirrels still need some immune response during hibernation, even if the animals are not active. "They're not hibernating in a sterile room. They are in a hole in the ground that has a lot of parasites, bacteria and other microorganisms." Studies by other researchers show that harmful bacteria can still grow in animals during hibernation, even in their lowered body temperatures.

That's one reason why it may be important for animals to periodically arouse from hibernation, according to Nelson. All animals that hibernate arouse at regular intervals -- from two to 30 days in different species -- during hibernation. These arousals use up to 80 percent of the energy an animal expends during hibernation, so they must have important functions, Nelson said.

Scientists have suggested a variety of reasons for the purpose of these arousals, such as the need to eliminate sleep debt (hibernation is not the same as sleep) and the need to clear wastes from the system.

"All of the various hypotheses have been challenged or rejected, so there has been no clear consensus," Nelson said. "This study suggests that one important reason that animals may need to arouse from hibernation is to recognize and combat pathogens in the body."

The study was supported by grants from the National Institutes of Health.

Anthrax drugs used to treat adults can treat children, too

The two drugs most commonly used to treat anthrax in adults could cause unwanted side effects if used in children, according to an analysis of pediatric anthrax treatment options. But the risks of using either medication pale in comparison to the risks of anthrax disease, said Milap Nahata, a professor and chair of pharmacy practice and administration.

"Anthrax can be fatal, and children may have the greatest risk for developing the disease in the event of a major bioterrorism attack," he said. "So the use of these antibiotics can be recommended despite the lack of adequate efficacy and safety studies in children." Children may have a greater chance of contracting the infection simply because their respiration is faster than adults and their skin is more permeable as well.

The researchers analyzed nearly 20 studies that examined the safety and efficacy of two medications -- ciprofloxacin and doxycycline -- when used in children. The drugs are also often used to treat adults with the disease. Past research links ciprofloxacin (sold under the brand name Cipro) to bone deformations and doxycycline to bone growth inhibition and tooth discoloration in children.

www.osu.edu/researchnews/archive/ciprodox.htm