During a flu-like fever, it’s natural to wonder why your body feels the chills, sweats, and aches that come with it. A new study offers insight into what’s going on beneath the surface. A fever-like high temperature alters the behavior of certain immune cells, boosting the activity of some key infection-fighting cells and reducing the inhibitions of regulatory cells by altering metabolism, the team says. the study Published in the Journal on September 20th Science Immunology.
The discovery offers insight into a long-mysterious biological process and helps partially explain how fever fights infection. But the new study may also shed light on the dark side of the immune response: the specific biological pathways the researchers identified may play a role in the increased cancer risk known to be associated with prolonged inflammation. In short, “a little fever is good, but too much fever is bad,” says the study’s lead author. Jeff RathmellProfessor of Immunobiology at Vanderbilt University Medical Center (VUMC).
Fever is a rise in whole-body temperature and is usually associated with infection; inflammation involves a more localized rise in body temperature and can result from injury or illness. We’ve long known that temperature is an important variable in many biological processes, but the function of fever—and what happens to the immune system when the so-called thermostat is turned up—is poorly understood, says Rathmell. “The science doesn’t have good answers,” he says. It’s generally thought that fever makes invading microbes—those disease-causing pathogens—less welcoming, but “we don’t really know,” he adds.
New research suggests the reality is much more complicated than basic explanations. There’s another side to the equation to consider: how our own cells respond to excess heat. Previous studies have shown that heat Supports the immune system By stimulating activity. This week’s study explains how it works, all the way down to the subcellular level.
Rathmell and his co-authors looked at how several types of T cells, a subset of white blood cells, respond to heat. In experiments with lab-cultured cells, they found that “moderate heat” — about 102 degrees Fahrenheit — increased the metabolism, proliferation, and activity of a group of general T cells, which differentiated into multiple immune functions. At the same time, regulatory T cells, which generally suppress immune responses, began to malfunction, a double negative result that meant the body’s defense system became less reined in.
Finally, and counterintuitively, the high temperatures stressed a type of helper T cell that’s important for fighting off viruses. Many of these Th1 cells died in response to the stress. But the cells that survived were super cells, faster acting and more proliferative. “The ones that survived had the adaptive capacity to overcome the stress. They’re better in the long run, but they have to overcome this obstacle along the way,” says Rathmell.
“That balance makes logical sense in the context of typical infectious diseases,” says the lead author. Darren Heintzman“You want your inhibitors to be worse and your effectors to be better,” says the VUMC postdoctoral fellow. But there’s a catch.
In subsequent experiments, the scientists zeroed in on the mechanisms behind many of the changes they observed. Cellular metabolism and mitochondria are crucial, especially a large metabolic protein called electron transport chain 1. This protein complex, which fuels cells, was much less efficient under high-temperature conditions. The same cellular stress that occurs in helper T cells is probably occurring throughout the body, where it can cause DNA damage in the mitochondria of various cells, leading to things like cancer growth. “When that heat and inflammation becomes chronic, it becomes a problem. In conditions like autoimmune diseases, that’s not a very good thing,” Heintzman explains.
Certain cancers, such as colon cancer, Associated with inflammation There is at least one clear hypothesis from intestinal diseases like Crohn’s disease: “The fever associated with local inflammation may be due to this mitochondrial mechanism… And ultimately, [cancer promoting] “Mutation,” says Rathmell. Popular Science.
But at this point, it’s just speculation, he adds. They have some data from the petri dish experiments and from past mouse and human studies that suggest their theory has merit, but more work in real living systems is needed to confirm the hunch. Studying temperature changes in animals is difficult because there are so many variables at play that it’s nearly impossible to isolate the effects of any one change, “but it’s something that’s really important, and we’re very interested in doing that,” Rathmell says.
“Anyone can get a fever. Everyone experiences changes in temperature. You feel swelling and a throbbing sensation. [injured] “Keeping your fingers warm is really important, both for cooling them down and for cooling them down,” Heintzman says. We now have a better understanding of how these thermal effects benefit and harm humans, he adds. That doesn’t mean you should always skip taking fever-reducing medication when you’re sick, or worry too much about a swollen sprained ankle, he says. But it does mean that even innate biological responses might be best kept in moderation.
