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."