Fever Can Be Beneficial for Recovery, New Study Finds

A new study by scientists at the University of Alberta sheds light on how a moderate fever can be beneficial when illness strikes. The research – conducted in fish – is published in eLife.

Fever across the animal kingdom

When fever strikes, it can be a sign that the body is fighting an infectious or inflammatory disease. An increase in body temperature is caused by the activation of thermoregulatory pathways via a highly organized immune response, the overall effect of which appears to enhance the body’s ability to defend itself and survive. The exact mechanisms by which this advantage is conferred are not wholly understood.

The new study, led by immunologist Dr. Daniel Barreda from the University of Alberta, aimed to gain additional insights into the immunobiology of moderate fever, a process that he describes as being “evolutionary conserved across the animal kingdom for 550 million years […] every animal examined has this biological response to infection.” When infection occurs, fish transition to areas of warmer water, whereas reptiles lay on sun-soaked areas of ground. In honeybees, infection even triggers behavioral thermoregulation at a higher level: the entire group will work together to increase overall hive temperature. “Despite different physiologies and thermoregulatory strategies, common biochemical pathways appear to regulate fever across cold- and warm-blooded vertebrates,” the researchers say.

Fever helps fish recover faster

Barreda and colleagues conducted their experiment in mixed-sex goldfish, which were infected with the bacterium Aeromonas veronii. “An in vivo Aeromonas cutaneous infection model was tailored to focus on the most common moderate self-resolving form of this natural biological process rather than severe pathological fever,” the researchers explain.

The fish were housed in an enclosure that delivered thermal gradient stability. “Infected fish were assigned randomly to different temperature categories,” the researchers note, which allowed them to compare the immune response and recovery in fish that could exert fever, to those that couldn’t.

The researchers tracked and evaluated the outward behaviors of the fish post-infection using machine learning and matched these behaviors to in vivo immune responses by collecting and analyzing blood and wound tissue. Overall, they found that “natural fever offers an integrative response that not only activates defences against infection, but also helps control it,” says Barreda. In fish that could exert a moderate fever, the infection cleared within seven days – half of the time required for fish that couldn’t exert fever to recover.

In addition, fever aided the fish’s immune system in shutting down inflammatory processes, and repairing tissues that had been damaged, a system that Barreda likens to the functioning of a car: “This works much like turning off a car, rather than leaving it running, after you are finished driving. It saves energy and prevents additional damage,” he explains.

“Our results reveal novel features of fever and demonstrate that it is an integrative host response to infection that regulates both induction and resolution phases of acute inflammation,” the research team describes, noting however that further work will be required to understand whether this process is conserved across both cold- and warm-blooded vertebrates. “Because the mechanisms driving and sustaining fever are shared among animals, it is reasonable to expect similar benefits are going to happen in humans,” Barreda adds.

Ultimately, Barreda and colleagues hope that their work can aid our understanding of when it is necessary to treat a fever. Certain medications can remove the discomfort of fever-associated symptoms, but could taking these drugs also adversely impact the “benefits” associated with the natural fever response?

Reference: Haddad F, Soliman AM, Wong ME, et al. Fever integrates antimicrobial defences, inflammation control, and tissue repair in a cold-blooded vertebrate. Medzhitov R, Rothlin CV, Flajnik MF, eds. eLife. 2023;12:e83644. doi:10.7554/eLife.83644.

This article is a rework of a press release issued by the University of Alberta. Material has been edited for length and content.