Hot and Cold: The Katy Perry Understanding of Fevers

Hot and Cold: The Katy Perry Understanding of Fevers

As I laid in bed for several days feeling like a truck had run me over and feeling like the Katy Perry song “Hot n Cold”, it got me thinking about a few things.

1. Why does a fever occur?

2. Should we allow a slight fever to help combat an illness?

Hot n Cold - Wikipedia

I feel like we all know what a fever is and have had A&P smashed into our heads enough; but there are some important factors to think about. Our Hypothalamus is our thermoregulatory center and is what fluctuates our body temperature to keep everything in happy homeostasis. When you develop an infection or get “the man flu” as my wife calls it, several processes occur.

Our Immune response is made up of macrophages, T cells, endothelial cells,  reticuloendothelial system, etc all notice that there is an issue and release IL-1, IL-6, and TNF which are pyrogenic cytokines (this process can also be triggered by the lipopolysaccharise (LPS)  parts of a bacteria cell). These reach our hypothalamus and cause an increase in prostaglandin E2 (PGE2) inside our hypothalamus. PGE2 will try to conserve and generate heat. To conserve heat, it will cause vasoconstriction. To generate heat, it stimulates thermogenesis by causing the stimulation of neurons that have the PGE2 receptor 3. These neurons cause a dump of norepinephrine which causes the thermogenesis of our adipose tissue (specifically our brown fatty tissue) and our muscle cells. The conservation of heat and the geneneration of heat shifts our set point temperature to be higher than normal which causes us to have a fever.

Now we know that we for some reason bundle up with 6 shirts, sweat pants, a sweatshirt, and hide under a mound of blankets when we get a fever which never made sense to me. This occurs because our heat sensing neurons are not as reactive so you start to feel cold. And acetycholine is produced which causes you to shiver and feel cold. So there is a behavioral part of the fever process. And we have this occur because of pyrogens. These are basically something that causes a fever and can be exogenous or endogenous.

So we know why we get fevered and we know that a fever helps our body by helping our immune system. A fever is also beneficial because some viruses and bacteria can’t thrive or survive in warmer environments and can decrease how fast they replicate. So should we treat all fevers the same? 

A study came out in 2011 and is linked below in the references and they found out that CD8+ cytotoxic T cells, which target and destroy viruses, actually perform better in a mild fevered (less that 102 F) state in comparison to a normal body temperature. They believe that this occured because the elevated body temperature impacts the T cells’ membranes and makes them more proactive and are able to destroy more viruses in comparison to normal body temperature. So a mild fever is a good thing. But what if the patient’s temperature is 102 F or even higher? Well we can give tylenol, NSAIDS, and corticosteroids. These block an enzyme called cyclooxygenase which decreases the amount of PGE 2 which in turn drops our set temperature and decreases our fever. 

 This site is meant to be used for educational use only. We strive to push evidence based medicine with no bias to help you obtain all the important information. You should always follow your protocols that have been set in place

– Scopeducation Team (Matt)


 Balli, S. (2021, August 28). Physiology, fever. StatPearls [Internet]. Retrieved January 1, 2022, from

Evans, S. S., Repasky, E. A., & Fisher, D. T. (2015, June). Fever and the thermal regulation of immunity: The immune system feels the heat. Nature reviews. Immunology. Retrieved January 1, 2022, from

Mace, T. A., Zhong, L., Kilpatrick, C., Zynda, E., Lee, C.-T., Capitano, M., Minderman, H., & Repasky, E. A. (2011, August 26). Differentiation of CD8+ T cells into effector cells is enhanced by physiological range hyperthermia. JLB. Retrieved January 1, 2022, from

Turman, M. V., & Marnett, L. J. (2010, March 17). Prostaglandin endoperoxide synthases: Structure, function, and synthesis of novel lipid signaling molecules. Comprehensive Natural Products II. Retrieved January 1, 2022, from

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