Vol. 17, No. 30May 7, 1998

Instinctive reaction

Research shows older rats seek heat to fight illness

Evelyn Satinoff (foreground), chairperson of the Department of Psychology, is one of the nation's leading researchers in thermoregulation. In a study directed by UD postdoctoral neuroscientist Maria Florez-Duquet (standing), Satinoff and Research Associate Elizabeth D. Peloso (left) found that young rats with bacterial infections move to a relatively warm part of an experimental alleyway, while older rats prefer even warmer positions, where they produce a fever.

Geriatric rats instinctively ward off sickness by huddling in hot spots, and ongoing studies of their behavior may suggest drug-free strategies to help older people fight infections, UD researchers reported April 21 at the Experimental Biology '98 meeting in San Francisco.

"Most older rats, like many older people, either don't get fevers or get low fevers when they have an infection," explained Evelyn Satinoff, chairperson of the Department of Psychology and one of the nation's leading researchers in thermoregulation. "While an extremely high fever may be life-threatening, especially for very young children, moderate fever is widely believed to be an essential tool in the immune system's arsenal. In most cases, fever helps the body combat dangerous pathogens."

Compared to young rats, older rats housed at room temperature typically get much lower fevers, but new UD data shows "they can get a fever when they're allowed to select the temperature of their environment," reported Maria Florez-Duquet, a post-doctoral neuroscientist at UD who authored the Experimental Biology paper, along with research associate Elizabeth D. Peloso and Satinoff.

If the UD research pans out, Satinoff said, it may ultimately help doctors more easily fight infections among older patients. Although Satinoff emphasized that the UD work is still preliminary, helping to combat infections "might be as simple as placing an older patient in a very warm room to induce fever," she said.

Heat-seeking rodents

Laboratory rats reach the end of their lives around 30 months of age, Florez-Duquet noted. By 24 to 26 months of age, older rats in Satinoff's experiments demonstrate a strong preference for heated areas. "If you're a lab rat with an infection," she said, "selecting a warm environment clearly is a smart thing to do."

To learn more about the drive to survive in older rats, the UD research team initially injected lipopolysaccharide (LPS), a fever-inducing component of bacteria, into a half-dozen animals aged 3 to 4 months, as well as an equal number of older specimens. When young rats were housed in a room-temperature environment (73.4 degrees Fahrenheit, or 23 degrees Celsius), they all developed fevers, but the condition was rarely apparent among the older animals, according to Peloso, who co-authored early UD findings with former post-doctoral researcher, Maciek Wachulec and Satinoff.

Satinoff suspected, however, that the older rats could develop fever if they were provided with greater control over their environment. So, UD researchers placed tiny transmitters in the abdomens of young and old rats, then recorded and analyzed their behavioral responses to LPS injections. Each animal was placed in a long, box-like alleyway that was cooled at one end and heated at the other end to provide a range of temperature choices, from 50 to 104 degrees F (10 to 40 degrees C). The transmitter automatically measured each rat's body temperature every five minutes, while sensors located at regular intervals along the length of the alleyway recorded the animal's position every minute. All data was continuously fed into a computer for analysis. With few exceptions, "Young rats go to the relatively warm part of the alleyway, while older rats prefer even warmer positions," where they produce a fever, Florez-Duquet reported.

How much heat is needed to help older rats induce fever? The UD researchers have been trying to pinpoint an optimal fever-producing temperature by placing animals in cages heated to 68, 86 or 89.6 degrees F (20, 30 and 32 degrees C), Satinoff explains. Older rats do not develop a fever at 68 degrees F, but they develop symptoms of "perfectly normal fevers" in the two warmer environments, she said.

"The next step," Florez-Duquet said, "is to understand the physiological mechanisms that give older animals this ability to behaviorally regulate fever." The immune systems of young versus older rats may function differently, Satinoff said. Older rats may, for instance, have higher levels of particular stress hormones such as corticosterone, which inhibits fever. Or, they might have lower levels of interleukins, the immune-response factors that promote fever. An infection triggers the production of these and other chemicals in the brain, Satinoff noted, and complex neurological reactions may be mediated by exposure to heat.

"Our work has thus far been limited to a relatively small number of animals, and the implications for older people are still speculative," Satinoff cautioned. But information about fever regulation among older populations may provide new information for doctors, nursing home administrators and elderly people, she said, because fever is "an important component of the immune-system response."

The Experimental Biology '98 meeting was attended by more than 10,000 scientists from six of the world's leading scientific societies. This year's meeting in San Francisco was sponsored by the American Physiological Society, American Society for Pharmacology and Experimental Therapeutics, American Society for Investigative Pathology, American Society for Nutritional Sciences, American Association of Immunologists and American Association of Anatomists. Nineteen guest societies also participated.

-Ginger Pinholster
Photo by Jack Buxbaum