Submitted by Key-Marionberry-9854 t3_115uh6t in askscience
Sometimes when fighting off a virus, bacteria, injury, etc., the body fluctuates between elevated temperature (fever) and normal temperature. This causes a cycle of chills, sweats, chills, sweats,… Why does the body not maintain an elevated temperature until the “problem” is resolved.
To add to this, from the perspective of someone with biology training but not medical…
It is entirely possible that this is an evolutionary response. Fevers kill the disease and, if they go on long enough, the host.
It makes complete sense that a cycling fever provides the most likely survival of the host and that individuals that don’t cycle fevers simply don’t survive.
It's also worth mentioning that the human immune system is an insane rube goldberg machine where almost every pathway has multiple mechanisms of negative feedback regulation. It's almost universal that when your cells sense a cytokine produced by a viral infection, like interferon gamma, they respond to it (inflammation, fever, antiviral gene transcription, etc), but they also up-regulate genes that serve to dampen the cell's response to interferon. If you put a cell in a steady state amount of cytokine, it will usually have a strong initial response, followed by a damping of the signal. There are a lot of mechanisms by which this happens (down-regulating the receptor, up-regulating the inhibitors of the receptor, etc.)
Chaos into order, via evolution.
It's like a core metaphor for everything we are and know.
Yea it’s really cool to think about. Entropy is one of my favorite words.
I tried to explain it to an MFA once. It’s surprisingly difficult to describe in simple terms
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I like to imagine we are a little backwards swirl going to order in the grand big swirl pattern that overall tends towards entropy.
That's a good analogy really.
With all the random stuff happening, it's possible for things to order themselves by random chance. Earth life happened to order itself just the right way to self replicate and thrive on our island of stability where there are energy gradients to exploit.
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I am currently studying anatomy. Calling the body itself a rube goldberg machine sounds so accurate.
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Yeah, extended fevers lead to brain damage, which severely inhibits your ability to produce offspring.
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Given the current state of affairs, I’d argue that brain damage hasn’t seemed to inhibit that much reproduction.
They don't, actually. Fevers have to get up pretty high, to 107-108 to cause brain damage, which is pretty darn rare. I can count on one hand the number of fevers I have seen over 107.
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Lol I love this for some reason. “We done being on fire yet?” viral load shoots back up “nope.”
I believe so. Too high of a fever, or too long of a fever, your organs start to cook.
Side note: that's actually the reason why Ebola is so dangerous: its natural reservoir are bats who have higher body temperature than humans, so when the human body wants to get rid of it, it has to ramp up the fever. And since the virus can handle higher temperatures, the fever has to run hotter and/or longer to kill it off, but has a very high chance of cooking the internal organs as well.
Having a fever that lasts longer but doesn't kill you seems like a pretty good evolutionary trait tbh..
I thought it wasn't the fever that killed the virus but that the fever made your own immune cells better at defending against it because the higher temperature is a better environment for them.
It doesn't outright kill individual pathogens, but it does combine the effects of making it harder for them to survive (so letting the population die out) and increased production and activation of immune cells. But that doesn't mean it's a better environment for them than normal body temperature, as of course the system is designed to handle 99% of the infections in that condition. Fever really is the fallback scenario where all bets are off until they fix the issue, causing all the other effects we call 'being sick'.
Not that I've ever read. It's generally taught that it makes the environent less hospitable to viral/bacterial enzyme function and replication.
And it really slows down the rate that viruses multiply which allows your immune system to reduce the number of viruses that are able to multiply.
I've heard that white blood cells are about twice as mobile per degree C of temperature rise.
So, based on this, does taking a fever reducer (e.g. acetaminophen or ibuprofen) also reduce the fever, and/or the body’s ability to fight the virus?
To a certain extent, yes. You should take an antipyretic if your fever is high (above 39.8°C) and doesn't break. At least these are the recommendations I've always gone by myself. It just prolongs how long the body will fight off the virus. This is the same for cold and flu medicines.
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Right. If the fever would be at its height for the whole time, there would need to be a specific mechanism that stopped it when its not needed anymore. That's much more costly, in evolutionary sense. With a cyclical one, each fever is supposed to die on its own, so it's just a matter of trying again if the previous one didn't work.
And fevers are often just an attempt to mitigate until you can produce an adequate antibody response
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You guys are so bloody smart. I thank you for your time sacrifices for the betterment of our society. Scientists honestly deserve glory only reserved for humanitarians and warriors.
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lol. well arguably, if the fever does not injure you then it will clear the virus faster yes. Unfortunately evolution is a case of what does not prevent reproduction as opposed to what is most optimal. Fever kills virus, but it also can injure the host. General rule - don't reduce fever unless the fever is dangerous. (if clearing the virus is the top priority- generally survival is top prioirty and its preferable to manage the fever and prolong the illness slightly. ) - disclaimer, not medical advice.
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Sounds like a classical control feedback loop in engineering.
However if it was just this there'd be no reason the body wouldn't have developed some kind of hysteresis to "debounce" the system, latching the fever on for a period after the viral load drops to ensure the complete eradication of the virus.
I suspect the fever is expensive or damaging in itself. So the best system is something less drastic, but that might take longer to kill the virus.
There also isn't a reason to think the body would evolve a way to stay in fever after vital load drops. Remember, evolution is random and if this never randomly occurred we wouldn't evolve it.
It's random in the short term. In the long term, beneficial traits will improve survivability and be selected for. If staying in fever benefitted surviving it's reasonable to assume it would have arisen by chance and then been selected for by now.
Be careful saying that beneficial traits will necessarily become more prevalent. It's all probability. If getting the long-term better trait necessitates going through a worse trait in the short-term, it may never happen. As an example with arbitrary numbers, say staying in fever another 1 to 5 hours is actually disadvantageous, even if staying 5-10 hours is advantageous.
True. Local inflections like that can act as barriers to getting to a much more advantageous trait. I agree.
...but I also think it's wrong to say evolution is random. It's random experiments in a game of procreation. Those experiments which fail are discarded. As such the overall process is guided away from failure and not random.
Maybe I was asserting the positive case (towards success) too much, when the negative case (away from failure) is really the stronger aspect.
I had just wanted to add to your last comment, I think we are in violent agreement here! Saying evolution is "random" is simplified to the point of inaccuracy—I would say it is probabilistic.
There is definitely something to be said about going towards success. I'm thinking of the RNA world hypothesis about the origin of life wherein RNA molecules both held replicable genetic information (as DNA does) and catalyzed the chemical reactions to replicate itself. The self-sustaining molecules won out because... they sustained themselves. Life now is pretty damn good at "being successful", except when it's threatened by other life being more successful, which looks like moving away from failure.
You are correct but are missing the forest for the trees as they say.
The original mutation is random, benefiting (or at least not harming) is selected for. So without the random mutation there isn't anything being selected for.
For example, say we need to change gene 1 from A to C for the fever to last 1 hour longer (this is very simplified of course) but throughout history no one has changed gene 1 to C then there will be no longer fever to select for.
We can't see evolution as something that moves creatures along with intent. Nothing is guaranteed since you must first have a random mutation to progress.
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I suspect that the Lotka–Volterra equations would be applicable in this case.
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How long does a fever cycle typically last? Are we talking like every 15 minutes, or every few hours?
Defintely every few hours for a cycle. Tylenol will dampen the ups and downs
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That just sounds like a second-degree differential equations with extra steps.
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Mmm..no, it's probably not a caloric constraint. Being hot is pretty damaging to the host as well.
Maybe you should source the calory thing?
Starving to death is arguably more damaging than a fever, with the odd occurrence of infections that prompt a fever high enough to be lethal.
https://www.hindawi.com/journals/ijeb/2015/179791/
Closest link I can find talking about calorie restriction vs inflammatory responses.
It makes a lot of sense though. We practically have nothing left to adapt to, at least not on a major level. Our last big changes were at a point where food wasn't a daily guarantee, but getting some kind of injury or infection was pretty likely.
Our ancestors that could fight off an infection long enough to get to the next meal, or at least survive long enough to reproduce are, imho, the better candidates for passing genes compared to those that just kept trying to "burn the infection out."
1000yrs ago, just hanging around spending all your fuel for what amounts to no forward momentum in the survival game was probably a fast ticket out of the gene pool.
This is the worst kind of amateur take.
Humans have generally had a few days to weeks of fat reserve plus some extra weeks with muscle. The calorie cost of raising your temp 4°F is low. Plus, we have, since becoming human and probably long before, lived in groups (often familial) that help each other.
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Biochemical feedback systems mean that basically no part of your biochemistry is static on or off, but constantly in flux. The chaotic interactions of these feedback loops mean you'll have surges and ebbs in just about every process, including body temperatures during infections.
Is there fever calculus?
Your immune system has rhythms. There are a whole zoo of different immune cell types in your blood. The immune system is like a bunch of liquid organs, each with many cell types. Many cell types which are derived from bone marrow have a tendency to return to the bone during the day. They go home. Circulating cells found in a blood draw, such as neutrophils, can increase by 2 fold at night. At night more immune cells are on active duty.
In addition to the answers regarding pathogenic loading, the circadian rhythm of the body plays a role in both temperature regulation and, it's suspected, may interact with the pathogen: https://doi.org/10.3389/fcimb.2019.00425
I'd also add that, for the malarias, they tend to fall into cycles of synchronisation in their reproduction with points where they're more exposed to the immune system (free in the blood) coinciding with the most severe portion of the fever (made worse by the preceding hemolysis).
Homeostasis! This is a pillar of human biology.
There are several systems working entirely independent from each other.
The system responsible for keeping you at normal temperatures will act independently. Weather you are sick, exercising, or spending the day at the beach— if you are hot, it wants to turn it down. It’s toolbox includes things like sweating or sending out chemicals. The hotter you get, the more this system will ramp up to turn it off.
The immune system will also act independently. Thankfully, the immune system is very smart and can learn when to use its tools, including inducing a fever. The tools of the immune system and how it’s used is an entire field of study.
Whether it’s the course of an illness or walking in and out of shade on a hot day, your body systems will compete with stronger and weaker signals depending on how important system feels it needs to use their toolbox.
Understanding how each system works and being able to identify when things go out of whack is pretty much the field of medicine.
In many instances, pathogens display antigenic variation. Your immune system makes antibodies in response to pathogenic antigens, but some pathogens display a survival technique wherein they swap out their antigens so that the antibodies your body just made don’t work anymore. Sometimes this is a built-in mechanism, such as in relapsing fever. The pathogens in this instance are some species of Borrelia, where it can rearrange its DNA to dodge your immune system. Plasmodium, the family of protozoa responsible for malaria, also displays this strategy, and also has a characteristic presentation of cycling fever (which is two or three days depending on the specific species). In other cases it can simply be random mutations that result in cycles of fever due to selective pressure, wherein your immune system kills off pathogens with one antigen, leaving the pathogens with other antigens to proliferate. The Hepatitis C virus is good example, which even has an RNA polymerase that can't proofread gene copies, effectively encouraging mutations. Your body therefore goes through periods where it makes antibodies against a certain antigen (which can take a few days), kills off pathogens with that antigen, leading to reduced symptoms, but then leaves a few that switched antigens. The survivors proliferate and force your immune system to have to make different antibodies, repeating the process.
> Plasmodium*, the family of protozoa responsible for malaria, also displays this strategy, and also has a characteristic presentation of cycling fever (which is two or three days depending on the specific species).
An infectious disease specialist at my hospital said he never saw this kind of precise cycling in malaria patients, even though he treated hundreds of them. It seems to be one of the text book myths that float around medicine since forever.
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There are a lot of signals controlling inflammation and fever. But one of the simplest explanations is cortisol. Fevers tend to spike at night when cortisol levels are low but subside in the morning when cortisol levels are highest.
Is this the thing where the immune system evolved to become more active at night because then we rest anyway - no resources needed for walking around and hunting etc.? (which would then be achieved through cortisol levels)
It is worth noting that not all fevers are cyclical.
It is also worth noting that not all fevers are related to viruses, In fact, as much as you can generalize, viruses are less pyrogenic than bacteria or other parasites.
It is also worth thing that while chills and sweats may cycle, this is not related to core body temp in any consistent way.
One of the reasons why chills and sweats alternate is that pyrogens alter the actual temp set point in hypothalamus . So it is more akin to setting your thermostat on your central heating to 80 and setting your AC to be at 80 also.
It is also worth noting that in many bacterial infections that cause fevers, some or most of the pyrogens are released by your own immune system , these are not really related to bacterial reproductive cycles in many cases in any functional way.
So a lot of people here are explaining phenomena that don’t really occur are are not occurring the way they describe.
Malaria has truly cyclical fevers that are related to the blood levels of parasites .
However, people who survive malaria and have cleared infections often have periodic fevers.
Before antibiotics, many people who once had some kind of fever and survive, often had periodic fevers for most of the rest of their lives, in a way that would also be unrelated to cycles of parasite reproduction the way people are talking about it here. The biographies and autobiographies of the colonial era explorers and geographers and botanists are useful in this regard.
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>It is also worth noting that in many bacterial infections that cause fevers, some or most of the pyrogens are released by your own immune system , these are not really related to bacterial reproductive cycles in many cases in any functional way.
This is true. There are some exceptions- see Relapsing Fever. But most bacterial infections I'm aware of, the pathogen load isn't a major determining factor, but rather your immune response.
Some pathogens produce pyrogens and some are produces by the immune system.
Pathogen load is not a major factor per se in many of these. There are always exceptions. Some viruses produce high fevers and some bacterial infections low or none, but as a general rule viruses don’t really activate the arm that produces high fevers they same way and extra cellular invaders. Also as a general rule, it doesnt follow the life cycle of the organism, Also with some notable exceptions, malaria being one of them.
Medical knowledge here: to add on to what others have said, if your body stays at a high enough temperature for a prolonged period of time, there begins to be damage from it. Hearing loss, brain damage, seizures, vision loss, etc.... It has to fluctuate to keep the body alive aka homeostasis.
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I can't say that was ever discussed during patophysiology.
One case which I can speak about is malaria. There, it is due to Plasmodium's life cycle. It takes 3 days for them to mature in a cell. So day 1 they enter the cells, they 4 they burst the cells open, which releases all its crap simultaneously from many cells. Day 7 it's hatching time again etcetc.
I reckon there's also 1 with 4 day life cycle.
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Specifically in the case of Malaria, the fever bouts come and go because the parasite migrates between the centre of your body and the periphery, depending on whether it wants to be picked up by mosquitos. Besides this, it changes its immune epitopes on the reg, trying to fool your immune system which attempts to learn but gets confused by the constant changes on the surface of the parasite individuals.
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Adding to what already has been said, Cortisol levels fluctuating thanks to the cyrcadian cycle also have a saying in this. It acts as antinflamatory during the day, leaving you rekd at night to cope with the matter.
Is there a way to increase cortisol levels naturally without having to take prednisone, for example?
A very high fever can kill you in a fairly short amount of time in pretty nasty ways. You can go for weeks without eating. If you are staying hydrated and have no antibiotics or antihelmetics or anti malarials etc the slight increased calories (really, did you do the math?) is a no brainer against whatever immune benefits you get from killing off what is likely the major source of death until recent times (infections). This is very much forward momentum in the survival game.
The body's cyclical fever response is not fully understood but is thought to be a result of the body's attempt to fight off the infection or injury. The fever response may help to activate the immune system and inhibit the growth and reproduction of some pathogens.
As above people have discussed - I often tell parents this with their kids, to reassure them re swinging fevers- that’s it ok and it’s the immune system doing it’s job. However- I also say, and please correct me if I’m wrong- that from current trial evidence, when groups treated with anti pyretics vs no anti pyretics are compared- there is not a significant difference in length or severity of illness… anyone know if I am talking out of my rear here??
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fack_yuo t1_j93qfy2 wrote
as your body fights off the virus the viral load drops, the fever reduces, the body becomes more hospitable for the virus again, the virus is reproducing in cells teh whole time, the cells burst, the viral load shoots up again, the body responds with more fever. I'm sure someone will explain it in more detail but as i understand it thats pretty much it. viral load goes up and down which causes symptoms to be cyclic.