Qing Chen and Daniel Fisher, Roswell Park Cancer Institute

Hot and sticky.
In mice with an artificial fever, more lymphocytes (green) adhered to blood vessels (red) in lymphoid organs and crossed the vessels into lymphoid tissue.

Don't Fight the Fever

Jocelyn is a staff writer for Science magazine.

Nobody likes coming down with a fever, but feeling hot may do a body good. Researchers report online 5 November in Nature Immunology that a fever in mice revs up the immune response by helping white blood cells enter lymph nodes, where they join the battle against microbial invaders.

All mammals can develop fever when they're sick enough, and even cold-blooded animals with infections, such as fish and lizards, will seek warmth to raise their body temperatures. This suggests that fever somehow helps the body conquer the bugs. Immunologist Sharon Evans of Roswell Park Cancer Institute in Buffalo, New York, and coworkers are studying how fever affects the movement of white blood cells, or lymphocytes, from the blood into lymphoid tissue, where they learn to recognize and fight pathogens. Lymphocytes constantly circulate through blood vessels within lymph nodes and other lymphoid organs, but only some actually enter lymphoid tissue by crossing the walls of the vessels, known as high endothelial venules (HEVs).

Fever increases blood flow, which means more lymphocytes flow through lymphoid tissues. Evans' team had previously shown that fever also assists the passage of lymphocytes into lymphoid tissue, but they hadn't figured out what was happening on a molecular level.

So Evans and collaborators at Harvard University and in Germany gave healthy mice artificial fevers. The researchers put the mice in a warm chamber for 6 hours, which raised their core temperature 2.7 C degrees above normal, to 39.5 C (about 103 F). Then they injected the mice with lymphocytes labeled with a fluorescent dye. When viewed under a microscope, the warmed mice had more lymphocytes sticking to their HEV cells. As a result, twice as many lymphocytes as normal passed into the lymphoid tissue. The explanation: Heat caused the HEV cells to express on their surface higher levels of two so-called "homing" molecules, ICAM-1 and CCL21, which make lymphocytes tightly adhere to the HEV cells.

The new study "adds to our knowledge about why fever might be beneficial," says immunologist Andrew Luster of Harvard Medical School in Boston, who wrote an accompanying commentary. He says the findings could lead to new drugs for boosting the immune response against infections and cancer and for dampening inflammation in autoimmune diseases such as arthritis.

So what to do when fever strikes? That depends, says Evans. While fever might provide some benefit, it can be dangerous in children, and parents should follow a doctor's advice, she says.

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