Sickness, like pain, is a general concept, independent of any one specific disease.

"Sick animals behave differently," said Gregory Freund, associate professor of pathology at the University of Illinois at Urbana-Champaign. "You even see it in fish - the sick fish doesn't hang with the herd."

More formally, he calls sickness behavior "a set of highly conserved behavioral priorities" that speeds recovery from illness.

In the Oct. 18, 2005, issue of the Proceedings of the National Academy of Sciences, Freund and his colleagues from the University of Illinois at Urbana-Champaign and the Centre National de la Recherche Scientifique in Bordeaux, France, illuminated the relationship between sickness, diabetes and neuroimmune system function.

Sickness can be induced by lipopolysaccharide or LPS, a molecule present on some bacteria. LPS activates the production of cytokines, which are responsible for the run-down feeling of sickness.

The effects of LPS, in turn, can be reduced by insulin-like growth factor, or IGF. The research began with the observation that an IGF mimetic, vanadyl sulfate, could reduce recovery time from sickness (measured as mice's unwillingness to "hang with the herd," or engage in exploratory behavior toward other mice) by up to 50 percent in both normal and diabetic mice.

Surprisingly, however, vanadyl sulfate's effects were not due to a reduced production of cytokines. At least in the periphery - that is, outside of the brain - the situation was quite the opposite. The researchers found increased levels of two inflammatory cytokines. In the brain, the situation was more complex: There, vanadyl sulfate reduced the levels of several cytokines, as well as increased levels of endogenous cytokine receptor antagonists.

Mechanistically, vandal sulfate appears to work by blunting the transmission of vagus nerve signals from the periphery to the brain; mice that were given both vanadyl sulfate and an appetite enhancer did not eat more than controls, which is a standard way of testing vagus nerve function. Freund summarized the team's findings as "an increase in inflammation with a decrease in brain-based neuroimmunity."

Another interesting point was that IGF itself was ineffective in attenuating sickness in diabetic mice, though it did work in normal controls. The scientists wrote in their paper that "this finding of functional IGF-1 resistance was surprising, in that the diabetic state appears to be significantly more associated with insulin resistance as opposed to IGF-1 resistance. Furthermore, it was previously unclear whether physiologic IGF-1 resistance even existed in diabetes."

In the experiments reported in PNAS, vanadyl sulfate needed to be given for at least a week to be effective, and even then, "it won't prevent [sickness] - it just improves recovery," first author Daniel Johnson told BioWorld Today. So at that point, it doesn't look like there will be a sickness-killer to complement the painkillers for quick use against 24-hour bugs.

Johnson expects pharmaceutical attempts to blunt vagal transmission to the brain, if they pan out, would come in the area of chronic conditions or anticipated medical events, perhaps as long-term regimen for the elderly to help them bounce back from illnesses, or to be given prophylactically before surgery. He did note, however, that "this paper is only about acute disorders," and how effective the inhibition of vagal transmission is in long-term conditions has not been tested. Vanadyl sulfate itself is sold as a dietary supplement and is supposed to control blood sugar, though Freund said that "in our model, that really didn't work" - possibly because the mice are too diabetic.

Freund noted that though their results were the opposite of what the scientists had initially predicted - in their case, that was a good thing.

"In research, sometimes you get lucky when things don't go exactly as you had expected," he said. "You might find something that's different from what you had guessed, but just as interesting - sometimes even more so."