If I had to choose the most counterproductive treatment for an infection, it would be trying to suppress the associated fever. Yet, this fever-fighting approach is widespread among both lay people and healthcare professionals.
It’s almost like a knee-jerk reaction. A person feels fluish and hot, and immediately starts taking something like Aspirin (acetylsalicylic acid), Tylenol (paracetamol/acetaminophen) or Advil (ibuprofen) in an effort to suppress the rising temperature.
If the temperature rises above a certain psychological level, such as 38 °C or 101 °F, people double down on the above antipyretics (fever reducers), as if the fever – and not the underlying infection – was their current enemy No. 1.
In children, the temperatures often go above 40 °C (104 °F) during infections, so parents are even more eager to use antipyretics, seeing the fever as something their kids should avoid at all costs.
Most parents know that acetylsalicylic acid could be harmful to children, so they feed their kids with paracetamol or ibuprofen, as if these substances have no side effects.
This anti-fever attitude is so widespread that it even has a special name – fever phobia, popularized by an American pediatrician Barton D. Schmitt in his 1980 article on the topic.
As with any phobia, also the fear of fever is based on a highly inflated perception of the associated risks, which leads to a complete disregard for the vital importance of fever in fighting infection and other diseases.
Now, you might think I’m exaggerating. If fever is so important, why are so many people and doctors fighting it then? Well, the term “fever phobia” explains it – have you heard of any phobia being rational?
But don’t take any side yet. Let me tell you a bit more about fever so you can decide whether it’s a good idea to suppress it or not.
The Role of Fever in Fighting Disease
The cornerstone of any infection is the multiplication of the pathogen, such as a virus or bacteria, in the host. Entering the host is one thing for the pathogen, but without heavy multiplication, there is no infection.
After all, most bacteria and viruses live in our bodies without us noticing, as the immune system keeps them in check. The outside environment is not sterile, so our tissues connected to the outside, such as the skin surface, airways, or digestive tract, are not sterile either.
Now, you probably know that very high temperatures used in sterilization kill viruses and bacteria. But these temperatures destroy all living forms, so clearly, that’s not a viable strategy to kill pathogens inside the human body.
For that, we have the immune cells, which kill pathogens by attacking and eating them, using various chemicals along the way.
Viruses and bacteria are adjusted to the normal temperatures of their hosts. For human pathogens, that’s a temperature around 37 °C (98.6 °F). Even just one degree above this level, the pathogens are outside their comfort zone. Two or more degrees above, even worse for them.
Most importantly, temperatures above 38 °C (100.4 °F) significantly slow the multiplication of pathogens, such as viral replication or bacterial cell division. That means the army of invaders your immune cells have to fight is considerably smaller.
Given that the multiplication of viruses and bacteria occurs in a geometric or even exponential manner, slowing down this process makes a huge difference! It also buys time for the immune cells to multiply. Numbers matter in any war.
But hey, aren’t the immune cells hampered by the high temperatures, too? No! Even more importantly, it’s the other way around – the immune cells work better and faster during more elevated temperatures.
That’s the beauty of specialization – since the immune cells are specialists in fighting pathogens, they’re far from their full capacity in times of peace or truce. To switch to military mode and work in overdrive, they need specific signals – and the increased body temperature (in other words, fever) is one of the main ones.
It’s as if the excess heat gives them extra energy to fight. They move more quickly, communicate more, multiply faster, and kill pathogens more vigorously.
Now, given what you just learned about the effects of increased body temperature, what do you think will happen if you suppress fever when your body is fighting an infection?
If you paid attention before, the answer is simple.
First, the pathogens will start multiplying more rapidly, since the body temperature returns closer to their optimal range. And second, your immune cells will be more passive, as the lowering body temperature indicates to them that the infection has been taken under control.
Will the pathogens multiplying more and your immune cells working less improve or worsen your odds against the infection? Will it shorten or rather prolong the duration of your infectious disease?
I hope there’s no need for me to answer those questions. But it gets even worse. Apart from lowering your chances again the current infection, suppressing fever also reduces your odds of effectively fighting your future infections. Why’s that?
Like other armed forces, also your immune system needs to train regularly. There are several levels of training, such as casual training or sparring. But as martial artists often say, the best training is the actual fight. For the military, it’s the war, and for the immune system, it’s fighting the infection.
As a dedicated member of the armed forces, how would you feel if you were called off every time the war started? If also others were told to give it a break while the ranks of opponents were multiplying? How would it affect the morale of the whole army?
And most importantly, will your army have a chance to get better at fighting its opponents? Experience the heat of war? Practice and reach the ultimate sophistication it is capable of? Or will it grow dependent on outside help?
It’s the same with the immune system. An improperly trained and inexperienced immune system makes a person more susceptible to infections, which often last quite long and have more severe consequences.
How The Body Regulates Temperature
Well, since fever is so essential, how does the body drive the temperature up? And how does the temperature go back down?
Imagine you want to increase the temperature in your house by 3 degrees. What will you do? If you’re lucky and have a thermostat, you just set the temperature on your thermostat 3 degrees higher. And you close all the windows so that the heat doesn’t escape.
Does your body have a thermostat? Amazingly, it has – and less surprisingly, it’s located in the brain. To be more precise, in an area of the brain called the hypothalamus.
The thermostat is usually set at a temperature around 37 °C (98.6 °F), but its maximum setting is as high as 42 °C (107.6 °F). This temperature range is usually more than enough to fight the pathogens inside our bodies.
Now, does your body have windows you can close? No, but it has countless capillaries in your skin that can be closed almost instantly. That will make your skin cold, but the goal is to increase the temperature inside the body, not on the surface. The skin will gradually warm up from the inside anyway.
The hypothalamus is sometimes called the “brain’s brain,” so the body doesn’t question its temperature setting. If the setting is at 40 °C, the body does everything to reach and maintain that temperature. The same applies when the hypothalamus says the temperature needs to go back to 37 °C.
But the body has only a limited number of ways to heat up or cool down.
To increase its temperature, the body starts shivering first. For the muscles to shake in shivers, they need to burn more energy, which generates heat. It’s a quick solution, but not a very effective one. A lot of the energy goes into muscle movements, so the heat generation is only indirect.
As a matter of fact, the body maintains its normal temperature of 37 °C (98.6 °F) mostly using just indirect heat, mainly from metabolism, so it must have something up its sleeve for direct heat generation. And that “something” is brown fat.
You’ve probably heard of it in connection with bears and other hibernating mammals, but people have brown fat, too. It’s abundant in newborns and still sizeable in adults, but its amount decreases with age.
The availability of brown fat is one of the reasons why children have no problems generating fevers over 40 °C, while adults rarely get over that threshold, and really old people are sometimes unable to have a fever at all.
On the flip side, your body cools down by opening the capillaries in the skin (“opening the windows”) but more importantly, by sweating.
For the liquid sweat to evaporate, it needs to absorb some extra heat energy, which in turn cools the body. So it’s actually not the sweating itself but the subsequent sweat evaporation that has the cooling effect.
Because of the limited ways to regulate the body’s temperature, behavioral changes are also very important. A person that feels cold seeks warm shelter, puts on warm clothes or a blanket, and drinks warm liquids. When hot, people take off unnecessary layers of clothing and seek cooler environments.
Adjusting The Thermostat
Knowing how to heat up or cool down the body is one thing, but how does the body know when to turn up the thermostat and which temperature to set it to? And when to reverse the course?
We’re back to the immune cells. They constantly patrol the body, and when they start “smelling” distinctive parts of pathogens, such lipopolysaccharides from bacterial membranes or viral RNA, they start releasing signaling molecules called interleukins, in particular interleukin-1 (IL-1) and interleukin-6 (IL-6).
The more pathogens, the more of these signaling molecules are released. Through the bloodstream, these interleukins make it to the hypothalamus, but they don’t turn up the thermostat directly.
Instead, they induce the synthesis of an enzyme called cyclooxygenase 2 (COX2). Try to remember its name, we’ll need it later! Among other things, this enzyme is responsible for producing a special substance named prostaglandin E2 (PGE2).
What’s so special about prostaglandin E2? Well, that’s the substance that effectively turns up the thermostat in the hypothalamus by binding to its PGE2 receptors. The more prostaglandin E2 molecules are produced, the higher temperature is set, with an upper limit of 42 °C.
But it also works the other way around – as the production of prostaglandin E2 molecules decreases, the control wheel of the hypothalamic thermostat is turned down, until it reaches the standard setting of about 37 °C. Simple but ingenious!
And in case you wonder – yes, there’s also an enzyme called cyclooxygenase 1 (COX1), but its synthesis doesn’t have to be induced by interleukins. It’s produced most of the time because COX1 is involved in the body’s standard “housekeeping” matters like protecting the gastric inner lining, proper perfusion of kidneys and production of platelets.
How Fever Progresses And Subsides Without Interference
When viruses or bacteria multiply in the body, immune cells sniff them out, release interleukins, and through the cascade described above, the hypothalamic thermostat is set to a higher temperature, such as 39 °C (102.2 °F) for example.
Since the body never questions the thermostat setting, the person fighting the infection immediately starts feeling cold and begins to shiver, despite having a normal temperature of 37 °C. Like the girl on the picture below.
Her surface capillaries close up, so her skin becomes cold, which anyone can feel by touching. The shivers subside relatively quickly as the affected person engages in warm-seeking behavior, and the body temperature gradually increases by burning brown fat.
There is no sweating at this phase. Sweating cools the body, so it would be a waste of energy when the body wants to reach the opposite. Energy is precious, even more so when your body needs it to fight infection.
Once the desired temperature is reached, the body maintains it for as long as necessary. It can be a few hours or a few days, depending on the severity of the infection. During this phase, there is usually no sweating, either – by touching the person’s skin, you feel something like “dry heat” instead. But there are a few exceptions.
If you heat your body above the thermostat level, for example by drinking a lot of hot tea and covering yourself with a blanket tightly, you will be sweating until your body cools down back to the preset temperature.
Also, the thermostat setting may fluctuate a bit, depending on the level of prostaglandin E2 production over time. These minor fluctuations could result in occasional light sweating due to the body temperature being slightly above the recently changed thermostat level.
What you’re waiting for is when you break a sweat for real, with significant sweating. This next phase of fever is a good sign!
It means that your immune cells reached a tipping point in their battle against the pathogens and signaled to the hypothalamus that the current high temperature is no longer necessary and can be turned down.
If the diminished temperature doesn’t lead to the resurgence of pathogens, the immune cells stop asking for the increased body temperature altogether, no longer needing that additional help. As a result, the body temperature returns to normal.
However, if there is a resurgence of pathogens, a new cycle of fever (usually shorter) is started, which goes on until the pathogens are defeated.
What Happens When You Suppress The Fever
Do you recall the enzyme I asked you to remember? Yes, it’s cyclooxygenase 2 (COX2), the enzyme involved in the production of prostaglandin E2, which turns up the thermostat in the hypothalamus.
I called your attention to COX2 because it’s the enzyme that’s targeted by fever-suppressing medicinal drugs. Whether it’s acetylsalicylic acid (Aspirin), paracetamol/acetaminophen (Tylenol, Calpol, Panadol) or ibuprofen (Advil, Brufen, Nurofen), they all inhibit cyclooxygenase 2.
As a result, when your immune cells send messages (interleukins) to the hypothalamus asking for higher body temperature, those messages are not adequately heard by the hypothalamus. They are weaker and less intense, as the final messengers (prostaglandin E2 molecules) are not available in sufficient numbers to relay the message.
This hampered communication results in a suboptimal increase in body temperature and equally suboptimal function of the immune cells, while making it easier for the pathogens to multiply in the body. Naturally, your chances of quickly fighting the infection are decreasing accordingly.
Apart from lowering your odds against the infection, inhibiting cyclooxygenase 2 also results in an energy-draining tug-of-war between the medicinal drugs and your body, constantly setting and resetting the hypothalamic thermostat.
After the initial rise in body temperature, the tablet of fever reducer causes the thermostat to be turned down, so your body starts cooling (sweating) to match the new temperature setting. Then the fever reducer starts wearing off, which turns the thermostat higher again.
So you take another tablet and start sweating again, only to see your body temperature rise after the last tablet’s effect wanes. Your body keeps heating and cooling itself, without ever reaching the optimal temperature needed to help your immune cells.
In addition, there are also many side effects of Aspirin, Tylenol, Advil and similar tablets. They inhibit not only cyclooxygenase 2, but also its older sister – cyclooxygenase 1.
If you remember the “housekeeping” roles of COX1, it’s easy to figure out that its inhibition can result in stomach cramps, insufficient urination and unusual bleeding. And that’s just scratching the surface of the long list of side effects.
Conclusion
Is there any point in suppressing fever? Given its integral role in fighting infection, it is a counterproductive strategy. Yes, you might feel a bit better for a while and experience less pain, but is that the main goal? Are you fighting fever or the underlying infection?
The focus should be on dealing with the infection itself, not on suppressing the body’s immune system by reducing fever. In case of severe bacterial infections, dealing with the infection may require using antibiotics, but that’s up to your doctor to prescribe.
There are also many natural antibiotics, such as raw honey, garlic or cinnamon (all three usually swallowed as part of a concoction) and oregano or thyme essential oils (typically inhaled).
Some people with fever phobia fear that the fever will rise uncontrollably if unsuppressed, eventually damaging their brains or other tissues.
This fear is unwarranted because studies show that the upper limit of 42 °C is strongly regulated by the body – as a matter of fact, the body temperature rarely reaches 41 °C and does not spiral out of control.
Another unsubstantiated fear relates to febrile seizures (convulsions associated with fever) in children.
While a few percent of children are indeed affected by febrile seizures, these seizures are not harmful to kids, only frightening to their parents. If it helps, you can think of febrile seizures as more intense shivers, which are also harmless.
More importantly, clinical trials and systematic reviews have repeatedly shown that antipyretics (fever reducers) are ineffective in preventing febrile seizures. As a matter of fact, by prolonging the infection through counterproductive fever reduction, you’re just extending the period during which the febrile seizures can occur.
So why do so many people or even doctors still attempt to suppress fever? As I mentioned at the beginning, the term fever phobia says it all. No phobia is rational.
But the more important question is: Who stands to profit from this phobia? The people succumbing to it? Of course not. We’re back to the Root Conflict of Interest in medicine and the profit-hungry pharmaceutical companies.
They’re making billions of dollars every year on selling antipyretics – in 2022, it was approximately $2.8 billion. They have absolutely no incentive to educate doctors and patients about the counterproductive effects of suppressing fever.
And no one else has to power and money to do so. In healthcare, money is made by selling and prescribing drugs, not by your immune system doing its job effectively.
This sorry state of affairs is reflected in the inconsistency of clinical guidelines for fever management – after reviewing 74 guidelines for treating fever in children, the researchers found that there is not even one recommendation on which all guidelines agree.
The good news is, however, that a growing number of clinical guidelines realize that fighting fever is counterproductive. Even the notoriously pro-pharmaceutical guidelines in the United Kingdom advise against using antipyretics with the sole aim of reducing body temperature in children with fever.
Hopefully, common sense will gradually prevail, and more guidelines will follow suit. When fighting pathogens, we should each join forces with our self-protecting and self-healing body, not undermine its time-tested defense mechanisms.
As an ally against infection, fever should be welcomed, not feared and suppressed.
