Public Release: 

Hormones Focus Of Study On How Responses To Infection Are Regulated

University of Illinois at Urbana-Champaign

CHAMPAIGN, Ill. -- When infection strikes, behavior often changes. Scientists studying how the body responds to infection or inflammation -- whether a pathogen is ignored or leads to sleepiness or loss of appetite -- are focusing on glucocorticoids, naturally occurring hormones.

University of Illinois researchers are looking at the pathway between the immune and central nervous systems, known as the hypothalamic-pituitary-adrenal axis (HPA), the suspected site of a molecular communications system that helps the brain assess infection and issue response orders.

"We tend to think of the behavioral response to an infection as a side effect, not part of the host defense," said Rodney Johnson, a professor of animal science. "The changes in behavior are actually part of a well-orchestrated defense that, together with other immunological and physiological responses, helps to rid the body of a pathogen."

Johnson and his colleagues in the U. of I. Laboratory of Integrative Biology reported on their research, funded by the National Institutes of Health, in recent issues of Physiology & Behavior and the American Journal of Physiology.

Researchers in the 1950s and '60s found that stopping the secretion of glucocorticoids by removing the adrenal glands from animals left them highly susceptible to endotoxins. Glucocorticoids were later found to have anti-inflammatory effects that kept the immune system from overreacting. Johnson's team wondered if glucocorticoids also have a regulatory role in behavior.

In one study, they identified a low dose of lipopolysaccharides (LPS), a molecule found on the membrane of Gram-negative bacteria, that stimulates the HPA axis, causing an increased secretion of glucocorticoids, but does not induce behavioral effects. The same dose of LPS given to rats missing their adrenal glands led to changes in behavior. When glucocorticoid pellets were given to compensate for the missing adrenal glands, illness-related behaviors were again avoided.

In a follow-up study, they injected recombinant interleukin-1B -- a cytokine that acts in the brain to induce sickness behavior and stimulate the HPA axis -- and found that glucocorticoids appear to modulate the effects of cytokines.

"Previous studies clearly indicate that glucocorticoids inhibit the production of cytokines. These results indicate that they also somehow inhibit the behavioral effect of cytokines," Johnson said. His team is now following a theory that glucocorticoids somehow reduce cytokine production by the brain's microglia cells, which, when subjected to LPS, produce interleukin-1B.

The findings so far do not offer the prospect of artificially managing sickness behaviors, Johnson said, "but they do provide us with some basic light on how the secretion of corticosteroids during an immune challenge acts as a protective mechanism that prevents the immune system from overreacting and causing profound disturbances in behavior."

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