By Judy Foreman, Boston Globe Staff, 02/29/00
When a lizard is injected with live bacteria, it crawls to a warm spot in the sun (or under a heat lamp in a lab) to raise its body temperature, not unlike someone with the flu burrowing under the covers.
In fact, lizards that are prevented from raising their body temperature are more likely to die than those who toast themselves, probably because the higher temperature - in essence, a fever - revs up the immune system to fight infection more aggressively.
Indeed, fever is such a basic response to infection that it's been demonstrated up and down the evolutionary ladder in everything from ferrets to puppies to insects.
Fever is also so "costly" in metabolic terms - in humans, each 2 degrees at Fahrenheit of fever raises heart rate 10 percent - that scientists think fever would never have evolved in the first place unless it did more good than harm.
So the question is obvious: Should we treat fever with drugs like Tylenol? Or is it better to just sweat it out?
Surprisingly, there's not much human research on this point, "which is amazing, given that this it the single most common question people ask their doctors," laments Dr. Randolph M. Nesse. Nesse is a psychiatrist at the University of Michigan Medical School who co-authored, with George C. Williams of the State University of New York at Stonybrook, "Why We Get Sick," a book that explores the evolutionary underpinnings of disease.
"For myself, I take Tylenol when I need to function and don't try to go ahead and have a fever," Nesse said. One study on chicken pox did suggest that reducing fever with Tylenol makes people "stay sick a bit longer," he added, but since lowering a fever also makes people more comfortable, the tradeoff may be worth it, he said.
Matthew Kluger, vice president for research at the Medical College of Georgia and a prominent fever physiologist, echoed that. "When I lecture to medical students, I tell them that, when in doubt, let fever run its course. But I'm the first one to grab a bottle of ibuprofen to feel better, even though I believe it's making the infection last an extra day or so."
And there are times - especially with children - when it's crucial not to ignore a fever, notes Dr. Michael Shannon, associate chief of emergency services at Children's Hospital in Boston.
Granted, unless a child - or adult - has a fever higher than 105 or 106 degrees for a long period of time, fever isn't harmful. "We treat it because it produces comfort; it makes the kids feel significantly better," he said.
But, in infants under 3 months old, the immune system is so immature that something like a urinary tract infection that might not be dangerous in an older child or adult could be life-threatening - and fever may be the only telltale sign.
Miserable though it can be, fever is actually one of the most elegant phenomena in biology. Far from being a sign that body systems are going haywire, fever is a controlled elevation of the "set point," or thermostat, for body temperature.
Just like a house whose thermostat is raised a few degrees, the body's set point is raised during fever. Once it's raised, the system keeps further fluctuations to a minimum, so that temperature hovers around the "new normal" of, say, 102 degrees F.
What's striking is how precise all this is, said Williams, emeritus professor of ecology and evolution at SUNY. Most of the time, humans "keep body temperature within a fraction of a degree of normal."
In fact, mammals in general have a normal temperature close to the human 98.6 F, whether they're polar bears on an ice cap or "something running around in the Sahara Desert that would be better off if it didn't have to keep itself so cool," he said.
When infection and fever do occur, body temperature continues to be tightly regulated. In fact, nature has designed a complex system to both initiate - and stop - fever. When an infectious organism enters the body, the immune system swings into action, pumping out chemicals called cytokines, specifically interleukin-1 (Il-1), interleukin-6 (Il-6), and several others.
These cytokines, also called "endogenous pyrogens" (or natural fever-makers) trigger a cascade of other chemicals, including prostaglandins, which act on a part of the brain called the hypothalamus to raise the set point. (The main mechanism by which aspirin lowers fever is by blocking this outpouring of prostaglandins.)
At the end of an illness, another set of natural chemicals called cryogens or anti-pyrogens come into play. These substances, specifically TNF, alpha MSH, and AVP, then damp down the fever-makers to lower the set point back to normal.
In the early stages of infection, the difference between the rising set point and actual body temperature "makes you feel chilly," said Kluger, the Georgia fever specialist.
Once the set point and body temperature are equal - that is, once the fever is established - you don't feel chilled anymore. The opposite happens when a fever "breaks" - the thermal set point goes back to normal, but the patient feels warm (and gets sweaty) until the body temperature matches the set point again. This raising and lowering of the set point makes fever different from other situations, such as exercise, in which body temperature is raised. Exercise can boost body temperature to 102 degrees F or higher, notes Scott Montain, a physiologist at the Army Research Institute of Environmental Medicine in Natick. But it doesn't change the set point. "It's just that the body temperature rises so it can dissipate the heat it's producing."
With fever, once the set point is raised, a number of metabolic processes speed up to fight infection, Kluger said. White blood cells get to the site of infection faster, and white cells proliferate more rapidly. Although some researchers speculate that higher body temperature might also kill bacteria or viruses directly, the big benefit, he said, seems to come from revving up immune response.
Although it's not always necessary to treat fever, people should see a doctor if fever is accompanied by vomiting, difficulty breathing, unusual drowsiness, or severe headache. A person who won't drink fluids or looks persistently ill even after the fever is lowered should also seek medical attention.
Seizures during a fever, too, are a reason to call a doctor, of course, though many doctors now feel that most fever-induced seizures are harmless (albeit traumatic to watch). Typically, febrile seizures do not cause brain injury or raise the risk of epilepsy; they are simply the brain's response to a sudden rise in temperature.
All of which suggests that, except in very young babies or extreme cases, fever is usually more part of the solution than part of the problem. That doesn't mean you have to enjoy it, or even eschew medicines to bring it down. But it does mean that, in most cases, you don't have to worry about it.
Judy Foreman is a member of the Globe staff. Her e-mail address is firstname.lastname@example.org.