How fever helps us fight infections

24 January 2019

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Fever is a classical clinical sign that doctors have relied upon for hundreds of years to diagnose infections...

But its history goes back far further than the 500 years since Galileo built one of the first thermometers, because humans, birds and mammals all respond the same way and run a fever when they develop an infection. This argues that the process of elevating body temperature by 1-4 degrees Celsius must have a strong survival benefit. But why should it? Now, thanks to a recent paper in the journal Immunity, by Chinese scientist JianFeng Chen and his colleagues at the Shanghai Institute of Biochemistry and Cell Biology, we’re a step closer to knowing the answer.

Infections cause inflammation in infected tissues. This attracts immune white blood cells, called leucocytes, which migrate into the inflamed and infected tissues as well as the nearby lymph nodes (or your “glands” as your granny would say) to discover what is going on and to fight the infection.

The immune cells arrive via the blood stream. Blood vessels supplying the inflamed tissues become “sticky” by expressing molecules on their surface lining cells. These provide chemical “toeholds” that the passing immune cells can grab on to, causing the cells to roll slowly along the vessel wall. As they do so, inflammatory signals coming from the nearby infection trigger the immune cells to switch on Velcro-like adhesion molecules called integrins. These enable the immune cells to hold tightly onto the vessel lining and then squeeze through gaps in the vessel wall to enter the surrounding tissue.

In their study, the Chinese scientists have added a new piece to the puzzle. They've discovered that body temperature also plays a critical role in this process. The integrins, they’ve found, work in partnership with a heat-sensing - or “heat shock” - protein called HSP90. When body temperature rises, HSP90 is activated, and can bind onto an integrin protein in the immune cells called a4-integrin. This causes it to change its shape on the cell surface, activating it to make it sticky. And HSP90 can actually bind and activate two of these a4-integrins at once, so there is an efficient amplification process, which further increases the stickiness.

Critically, if this process is blocked, infections readily become lethal, showing that it plays a key role in our body’s ability to defend itself. This new understanding also means that we might be able to exploit this process under circumstances where the immune system has become dangerously over-active. Stopping it might provide us with new ways to treat conditions like autoimmune diseases, for instance.

Overall, this is a neat way of explaining the benefit to the body of generating fever in response to an infection. So, next time you’re sweating and shivering with the flu, try to be grateful and remember that it’s for your own good...

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