When people get a fever, they often take medicine immediately to relieve themselves of the symptoms. However, one should wait for a mild fever to run its course before automatically reaching for medications, because this helps clear infections faster, a new study suggests.
The study, led by researchers from the University of Alberta, was recently published in the journal eLife.
Researchers conducted the study on fish, and found that untreated moderate fever helped the marine animals clear their bodies of infection rapidly, controlled inflammation and repaired damaged tissue.
Why were fish chosen for the study?
Moderate fever is valuable to host survival, but it is difficult to establish the mechanisms involved in warm-blooded animal models because there are strict programmes which control core body temperature and disruption of these processes leads to psychological stress.
Therefore, the researchers chose a cold-blooded animal: teleost fish. Teleosts are ray-finned fishes with a tail in which the lower and upper halves are almost equal.
The researchers chose teleosts because these animals offered natural kinetics for the induction and regulation of fever and a broad range of tolerated temperatures.
They used a custom swim chamber which could track the position of the fish and allowed for consistency in fish behaviours.
In a statement released by University of Alberta, Daniel Barreda, lead author on the paper, said moderate fever is self-resolving, which means that the body can both induce it and shut it down naturally without medication.
Barreda also said that the health advantages of natural fever to humans still have to be confirmed through research, but since the mechanisms driving and sustaining fever are shared among animals, it is reasonable to expect similar benefits are going to happen in humans.
Why should humans avoid over-the-counter fever medications during mild fever?
According to Barreda, humans should resist reaching for over-the-counter fever medications, also known as non-steroidal anti-inflammatory drugs or NSAIDs, at the first signs of a mild temperature.
This is because while NSAIDs take away the discomfort felt with fever, ones consuming them are also likely giving away some of the benefits of the body’s natural response.
Barred said that moderate fever has been evolutionary conserved across the animal kingdom for 550 million years, and every animal examined has this biological response to infection.
Animals often take other risks to reap the benefits of natural fever
Natural fever has so many benefits that some species, such as fish, reptiles and insects, are even ready to risk predation and decrease their reproductive success to move to niches with temperatures that induce natural fever.
The researchers gave the fish a bacterial infection, and tracked and evaluated their behaviour using machine learning.
What was observed in the fish allowed to exert their fever?
In the fish who were allowed to exert their fever, certain mechanisms, such as pyrogenic cytokine gene programmes in the central nervous system, increased efficiency of leukocyte recruitment into the immune challenge site, and improved pathogen clearance, were observed. A pyrogen is a substance that induces fever, and a cytokine is a small protein crucial in controlling the growth and activity of other immune system cells and blood cells, which means that a pyrogenic cytokine gene programme is a mechanism that instructs the body to create pyrogenic cytokines, or proteins that can provoke fever.
Immobility, fatigue and malaise were some of the outward symptoms in fish that were similar to those seen in humans with fever.
The researchers found that even when the fish were infected with bacteria that grew better at higher temperatures, allowing the fever to run its course resulted in improved pathogen clearance.
Barreda said natural fever offers an integrative response that not only activates defences against infection, but also helps control it.
Subsequently, fever inhibited inflammation and improved wound repair. The fish which were allowed to exert their fever cleared their infection in about seven days, which is about half the time it took for those animals that were not allowed to exert fever.
Researchers often use artificial mechanical hyperthermia, a process in which the body is heated to as high as 113 degrees Fahrenheit, as a model of fever. However, this process could not recapitulate all benefits achieved through natural host-driven dynamic thermoregulation, or the natural mechanism of fever.
What is the significance of the study?
The significance of the study is that veterinarians and livestock producers can use the findings to manage illness in animals.
The authors successfully developed a new experimental system to study behavioural control of body temperature in fish, and using this experimental paradigm, they uncovered the impact of body temperature regulation on immune defence and tissue repair.
The authors conclude that the study findings define fever as an integrative host response that regulates induction and resolution of acute inflammation. Also, the findings demonstrate that the integrative strategy of fever emerged before endothermy, or the physiological generation and regulation of body temperature by metabolic means, during evolution.
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