The role of fever in combating illness has been a subject of historical debate. Early perspectives, such as that of ancient Greek physician Hippocrates, suggested fever could aid recovery. Conversely, physicians in the 18th century often viewed fever as a harmful condition that required treatment.
Current scientific understanding identifies fever as a component of the immune system's response to pathogens, a phenomenon observed across various animal species. While evidence indicates that fevers can assist in resolving infections, the precise molecular mechanisms by which they provide this benefit have remained largely unclear.
Investigating Fever's Mechanisms
Sam Wilson, a microbiologist at the University of Cambridge, noted the existing gap in understanding the molecular impact of temperature on viruses. Two primary hypotheses regarding fever's action have been considered:
- The elevated temperature of a fever directly harms the virus.
- The heat enhances the immune system's function, or is a consequential, unavoidable byproduct of the immune response.
Wilson and his team conducted a study, published in Science, to investigate whether elevated temperature alone is sufficient to combat certain viruses, specifically in a mouse model.
Experimental Design
To isolate the effects of temperature from the broader immune response, researchers employed a specific experimental approach. They utilized influenza A viruses, selecting bird flu due to its adaptation to higher avian body temperatures, which are comparable to human fever levels. Bird flu typically infects the warmer gut environment in birds, contrasting with human flu strains that target cooler airways.
The team identified the PB1 gene segment within the bird flu genome, which enables the virus to thrive in warm conditions. This segment was subsequently integrated into a human flu virus, resulting in two nearly identical influenza strains: a standard human strain and a heat-tolerant variant.
Laboratory mice were chosen for the study because they do not naturally develop a fever in response to influenza infection. This characteristic allowed researchers to simulate fever conditions by housing specific groups of mice at slightly elevated ambient temperatures. The mice were then exposed to either the normal human influenza virus or the engineered heat-tolerant version.
Study Findings
Observations from the experiment revealed differentiated outcomes:
- Under normal laboratory temperatures, mice infected with both influenza strains developed illness.
- When housed at elevated temperatures, mice infected with the heat-resistant strain continued to develop illness. However, mice infected with the standard human influenza strain exhibited fewer severe symptoms, suggesting that the elevated temperature itself contributed to mitigating the infection's effects.
Expert Commentary and Implications
Daniel Barreda, a microbiologist at the University of Alberta not involved in the study, commented that the research supports the concept of temperature alone playing a significant and effective role in the body's response to infection. He also noted that the study does not exclude the possibility that fever concurrently enhances immune system function, particularly for viruses that may be less sensitive to temperature changes.
Joe Alcock, an emergency physician and researcher at the University of New Mexico, acknowledged the study's contribution but cautioned against direct extrapolation of results from mice to humans. He highlighted that the research adds to the increasing body of evidence suggesting an evolutionary purpose for fever. Alcock also raised questions regarding the routine clinical practice of immediately treating fevers with medications such as acetaminophen or ibuprofen for viral infections, posing an as-yet unanswered question about whether such interventions might impede the body's natural capacity to clear an infection. He acknowledged that in many clinical scenarios, treating fever remains an appropriate measure due to the potential for high temperatures to cause cellular damage.