KeywordsBody Temperature Skin Cancer Metastatic Melanoma High Fever Immunological Response
A controlled increase of body temperature, commonly as part of an inflammatory response to pathogens.
Fever represents one of a selection of “sickness behaviors” that occur in response to pathogens that have infiltrated the body (Harden et al. 2015). It was itself originally considered a disease, though now has long been recognized as a defense mechanism and an aspect of the immune system. However, the degree to which fever is beneficial or detrimental to the host is still widely disputed (Hasday et al. 2000). Accordingly, the treatment of fever is just as controversial, even after being practiced for thousands of years (Earn et al. 2014).
Matthew Kluger presented some of the early evidence for the benefits of fever in fighting disease. Kluger et al. (1975) gave evidence that lizards injected with Aeromonas hydrophila (a bacterium) were more likely to survive when their body temperature was elevated. As such, the increase in heat caused by fever is argued to aid the survival of the host by heightening the immune system and by reducing the growth of pathogens. Recent research, however, suggests that the effect of fever is more complicated than initially considered, as are the consequences for treating it (Harden et al. 2015).
Fever has remained a part of the immunological response of both vertebrates and invertebrates (Kluger 1986) for millennia (Evans et al. 2015). Its presence in such a variety of animals is indicative that a febrile response has been present throughout much of evolutionary history, with some estimates suggesting its existence for over 360 million years (Hasday et al. 2000). This extended presence suggests that fever provides an adaptive advantage to the host, as without this survival benefit, it is unlikely that it would be so prevalent today (Kluger 1986).
Further evidence suggesting an adaptive advantage conferred by fever is that the activation and maintenance of a febrile response are energetically costly. For each 1 °C increase in temperature, the body has to increase metabolic rates by 10 % (Kluger 1986). As fever generally increases body temperature by between 1 °C and 4 °C (Evans et al. 2015), this would confer a significant disadvantage to the host if there were no benefits for the energy expenditure.
Though fever appears to benefit human survival in the vast majority of instances, there are situations where a high fever can be dangerous to the host. Such examples include individuals with heart anomalies and pregnant women, the latter being linked to increased rates of birth defects (Kluger 1986). However, these cases are in the minority in comparison to the overall population, and as such fever still provides an evolutionary advantage in enhancing the chances of survival of the host.
As fever has been present throughout much of our evolutionary history, questions have been raised about whether treating fever is beneficial or harmful to the host’s survival. Antipyretics are treatments for fever, most commonly pharmacological within contemporary society, with examples including paracetamol (Harden et al. 2015). These medications aim to artificially reduce fevers and to ease the discomfort in the patient (Zitelli 1991). However, fever has remained a part of the immunological response in a wide variety of species, implying it provides an adaptive advantage. As such, there is potential for antipyretics to negatively impact the immune response of the body by removing the advantages provided by the fever.
Unfortunately, the degree to which the treatment of fever benefits or detriments the host’s defense mechanisms is still uncertain, with little definitive evidence to support either conclusion (Harden et al. 2015). The consensus within contemporary research appears to be that, in the majority of instances of fever caused by influenza, there is little evidence to suggest that the use of antipyretics is beneficial (Harden et al. 2015). Conversely, there is also little evidence that the treatment of influenza-caused fever is detrimental other than the potential for altering the inflammatory process (Harden et al. 2015).
There is, however, evidence of a detrimental effect of antipyretic use during the treatment of metastatic melanoma (advanced-stage skin cancer). This is the result of fever enhancing the production of natural killer and T cells during fevers, a benefit which is removed following the use of antipyretics (Køstner et al. 2015). The benefit of a high fever in this example is associated with improved survival rates due to the improved immunological response (Køstner et al. 2015).
Many species have evolved a pyretic response to invading pathogens over a course of millennia. Though fever has a high-energy cost to the host, the immunological enhancement it affords provides an adaptive advantage for survival. However, the overarching benefits and drawbacks of treating fever have received little empirical study. In treatment of conditions such as influenza-based fever, however, the current consensus suggests that there is little benefit gained from treating the fever. There are conditions where fever has been evidenced as boosting the immune response of the host, for example, melanoma and for critically ill patients.
- Earn, D. J., Andrews, P. W., & Bolker, B. M. (2014). Population-level effects of suppressing fever. Proceedings of the Royal Society B: Biological Sciences, 281(1778). doi:10.1098/rspb.2013.2570Google Scholar