How Fevers Help Our Immune System Hunt Down Infections

It’s an ironic fact of life that the symptoms of a cold or fever are actually our bodies’ attempts at a cure. Runny noses, high temperatures and vomiting are all strategies aimed at forcing dangerous microbes from our bodies so we can feel better again. But, how the elevated temperatures that so often accompany an infection help us recuperate has been something of a mystery.

“In spite of the fact that they are important to us, there remains very little understanding of what it is that fevers do to improve survival,” said JianFeng Chen, a cell biologist at the Shanghai Institute of Biochemistry and Cell Biology in China.“Understanding this could be important for people to fight against infections, allergy, autoimmune diseases, and even cancer.”

Now, Chen and colleagues have figured out how fevers unleash the immune system to fight off infections. The team’s work could mean new treatments that not only combat infection but also curb inflammation during allergic reactions.

Febrile Fighter

Fevers raise body temps anywhere from 2 to 7 degrees Fahrenheit. Fever’s protective effects may be in part because ratcheting temps up is sometimes more uncomfortable for pathogens than it is for us. Poliovirus’ ability to multiply plummets in the face of a fever’s heat, for example. But some research has suggested the scorching conditions might also flush out infections by setting immune cells in action. Chen and colleagues wanted to find out how.

Heat Shocked

The researchers isolated immune cells from mice and then put them in incubators set to a normal body temperature (about 98.6 degrees F) or a feverish temp of 104 degrees F. They found the immune cells that grew in the febrile environment produced a suite of molecules called heat shock proteins. One of these proteins, known as Hsp90, quickly set in motion a cascade of events that eventually directed the immune cells to the infection, Chen and team report today in the journal Immunity.

“During infection, this mechanism can enhance the [movement of immune] cells to… sites of infection and facilitate the clearance of pathogens,” Chen said.

“This pathway is critical for animal survival during infection,” he added. Indeed, disrupting the pathway with a mutation in Hsp90 impaired the ability of mice infected with Salmonella to fight off the infection, the researchers found.

The discovery suggests that therapies to raise Hsp levels could help fight infections, while lowering them could help those with allergies or autoimmune diseases by slowing down inflammation, Chen said.

It also points to some new advice for people with a fever.

“People should avoid using fever-reducing drugs immediately once they have a fever,” Chen added. Instead he recommends taking a fever-reducing drug only after several hours with a high temperature. That way Hsp90 has had a chance to mobilize the immune system to clear the infection.