Fever!

Most viral infections start out with the same general symptoms: fever, malaise, aches. Those are usually the sign of your immune system starting to fight back. Fever is one of our defense mechanisms, and while it can be quite uncomfortable it is very rarely dangerous. One of the common questions I get asked in my classes is whether it is good or bad to take fever reducing medicines when you are sick. Well, Im not that kind of doctor so I can’t really answer that question, but I can tell you what research has been done on the benefits of fever.

The adaptive value of Saturday Night Fever, caused by listening to Disco, remains unknown

Presumably, by raising your body temperature, you can do a better job of fighting off an infection. The higher temperature may make it more difficult for the pathogen to grow because it grows optimally only at normal body temperature, or it may help the immune system work faster (or both). Some studies in animals have shown that reducing fever results in increased growth of bacteria or virus in the infected animal, and other studies have found increased proliferation, migration and activity of immune cells.

Whatever the mechanism, it is clear that fever must provide some advantage. There are many studies that demonstrate that fever is beneficial in overcoming infection. None of these studies alone is definitive, however taken together, they do seem to support a role for fever in fighting infection. For one, the febrile response is highly conserved in vertebrates (even “cold blooded” animals) and many invertebrates. Some lizards, for example, will seek warmer spots to rest and as a result, raise their body temperature when infected. Fever is also energetically very expensive, requiring 20% more energy to maintain a temperature even a few degrees above normal. It would be unlikely for such an expensive mechanism to be maintained by natural selection if it didn’t have some benefit.

In addition to the evolutionary perspective, several studies in animals show that a fever of a few degrees correlates with better survival rate from infection. Being correlations, we must be cautious in over-interpreting this. Another good way to test if something like fever is useful is to get rid of it. Infected animals can be treated with anti-pyretic (fever reducing) drugs to see what happens to their recovery in the absence of fever. These studies typically show that animals treated with anti-pyretic drugs take longer to recover, and in some cases even to increased mortality. There are some problems with anti-pyretic studies however, and one of the major problems is that many anti-pyretic drugs don’t just reduce fevers. They can have other effects on the body, not all of which are known, and so we can’t always be certain that fever reduction is the reason for the changes in morbidity and mortality.

Of course, I also like to look at the pathogens themselves for hints of what our immune system is doing. They are pretty good at defending themselves against our immune response, so if we look at their defenses we can learn more about how we attack them. The poxvirus Vaccinia encodes a protein that blocks fever. This protein interferes with the function of interleukin-1B, a component of our own immune system that regulates fever. Animals infected with Vaccinia lacking that protein develop fever, showing that when the viral protein is present, the virus can prevent fever. However, interleukin-1B does many other things too, not just regulation of fever, so it is possible that the virus is blocking interleukin-1B for a different reason.

So it is highly likely that fever is good for fighting off infections, but this is not to be taken as medical advice to avoid fever reducing medicines. In the case of naturally occurring infections in humans, we need much more research into fevers resulting from specific infections to decide when a fever is beneficial and should be left alone, whether the fever is dangerous, or if the fever is helpful but the risks of taking an anti-pyretic are worth alleviating the uncomfortable symptoms.

References:
Kluger, M.J. (1996) The adaptive value of fever. Infectious disease clinics of north america. 1(10):1-20.
Alcami, A. and Smith, G.L. (1996) A mechanism for the inhibition of fever by a virus. Proc Natl Acad Sci. 93:11029-11034.

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6 Responses to Fever!

  1. David Esteban says:

    yeah, I would think that that level of energy expenditure would account for much of the fatigue associated with fever and infection. As long as you can get supportive therapy (fluids, rest) its not likely to be a problem. It would be interesting to see if fever is actually more harmful in places where clean water or other simple supportive therapies are not avialble, or in people who are malnourished to start with.

  2. David Esteban says:

    I think the question of when a fever is too high has to be addressed for each different infection. What may seem to be harmful in one case might be helpful in another. Isaiah’s link below is a great example of when we think a fever is too high or is detrimental, when it clearly is beneficial in fighting the infection. The other question is, what is meant by “too high?” Presumably a fever that is too high is one that would be harmful to yourself, but actual harm from fever is exceedingly rare. Even febrile seizures are rarely harmful, they’re just frightening.

  3. Jackson Miller says:

    I think it’s especially interesting how our bodies expend 20% more energy to maintain a fever. I take it this is why fatigue may accompany sickness (although I’m sure other reactions in the body cause it as well). This also makes sense why having a fever that is too high could cause serious body damage and possibly mortality- because the body expend an enormous amount of energy (as well as other parts ceasing to function correctly I’m assuming). I would be interested to see if there are certain viruses that have evolved to take advantage of the increase in temperature, rather than suppressing it like Vaccinia.

  4. Haley Dusek says:

    So I understand that fever has its advantages, and that it is a proven defense mechanism; but how do we know when a fever is too high? At what point is the fever doing the rest of our body more harm (i.e. dehydration etc.) than it is helping with the infection. I realize that this question should probably be directed to a doctor, but I, as it seems you did too, found a hard time justifying one solution over the other because of the unknowns.

  5. Christian Aguado says:

    Wow, I always thought that a fever was caused by the virus but I didn’t think it might actually help your body fight it off. That’s pretty cool.

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