Fever is one of the best and oldest defenses that the human body uses to protect itself. Whenever there is a sharp and sudden rise in body temperature, one knows that he or she is infected, and the body has initiated its defense response.
These days there are many modern drugs used to suppress ever, but modern science does not allow their misuse. They are only useful when used sparingly, and when the fever is too high, and starts causing collateral damage. Otherwise, recommendations say that the fever should not be suppressed. Moreover, fever also serves as a symptom or biomarker regarding the severity of the infection.
Fever is not some fault, the brain raises body temperature, when under threat, in a very controlled manner. This means that the various brain centers control the rise in body temperature. This rise in temperature helps initiate many defensive mechanisms so that the body can protect itself better.
It is not just humans; fever is also used by many other species to overcome infections. Researchers think that it is an ancient way to protect the body. Humans and many other species evolved to defend in this particular way.
This article looks in detail at all how fever may help save a life, kill pathogens. This phenomenon is especially vital to understand to protect lives from seasonal infection or flu, or more severe diseases like novel coronavirus.
Before trying to understand the role of a fever in defense against viral infections, let’s understand why it is so difficult to defend against the viruses. And how do all the new viral infections keep emerging?
Viruses are often described as something in between living and inert materials. Viruses cannot replicate or reproduce on their self. They need to penetrate cells of other species to replicate. Once inside the cell of other species, they highjack their genetic material to produce their copies.
Viruses cannot just replicate in any living cell; each variety can enter some particular types of cells. That is why some infections may cause respiratory disease other diarrhea.
This also means that viruses are dependent on other living beings for replication and existence. They cannot stay in the outside environment for long. Thus, they need to be good at continuously finding new hosts for replicating.
Viruses are also good at overcoming host immune defenses for a number of reasons. Due to their small particle size, they are challenging to identify. But more importantly, they keep mutating or changing their identity (antigen structure). That is why one may catch seasonal flu multiple times, even in a single season. Human immunity takes too long to identify a viral attack in most of cases.
Additionally, viruses keep trying to replicate in new species, always looking for new hosts. Most such attempts fail, as they are identified and killed. However, sometimes, once in a billion times, they do succeed in replicating/infecting the new species of animals. This is how new infection comes into play.
Non-specific and specific immunity and role of a fever
The body uses non-specific and specific methods to defend against infections. Non-specific methods include physical barriers like skin, mucus. Non-specific immune cells like macrophages, neutrophils would attack any alien body. The non-specific defense is the first line of protection.
The second line of protection is specific immunity when the immune system identifies the pathogen and produces a specific response. This response could be in the shape of humoral immunity, which is producing antibodies that kill viruses, or non-humoral when t-cells mark the foreign antigens for destruction by various cells.
Fever can help stimulate both non-specific and specific immune responses. It may slow down the replication of viruses in a non-specific way by causing them direct thermal damage, or it may help immunity identify the intruders faster in several ways.
There are at least four known ways in which high body temperature may help fight various pathogens and viral infections.
1. Directly neutralizes pathogens – through thermal damage to viral proteins
Many microbes are highly sensitive to temperature. Many bacteria and viruses can only thrive at the usual body temperature, and even a couple of degrees of change is enough to kill them. It may happen as most microorganisms evolved over the millions of years to thrive at a specific temperature.
Studies show that many bacteria like N. gonorrhoeae, S. aureus, E. coli, would not survive long with a little rise in temperature.
There are many examples in nature when various organisms use heat shock to kill the invaders. Just take an example of bees; they can raise the temperature of their hive to kill invading wasps. They also use thermal shock to overcome fungal infections.
Additionally, studies show that, if in lab conditions, animals continually get medications to lower fever, they will have a lower ability to fight infection and thus survivability. That is strong experimental evidence in favor of the role of high body temperature.
Many people nowadays have a habit of using medications like aspirin, paracetamol, as soon as they have a fever. Research shows that it may not be a good idea. Abusing antipyretic drugs may do more harm than good, and people should learn to tolerate fever a bit.
One of the systemic reviews pooled data from eight studies to understand the risk of reducing fever with antipyretics. The study found that by using fever lowering medications, the risk of mortality increased by 1.34 times in animals infected by influenza.
This does not mean that one should never use paracetamol or aspirin, but one should be careful. Better avoid these medications until or unless the temperature is too high (like above 40 or even 41 degrees Celsius). Sometimes, prolonged high fever may do more damage than good.
2. Induction of protective heat shock responses – thus helping protect body cells
Researchers noticed that in most mammal fever results in a 1.5 to 5 degrees Celsius rise in body temperature. This similarity shows that this additional heat must be helping in other ways too. It may have some kind of essential and universal role in protection.
Science identified that a rise in body temperature induces the production of heat shock proteins (HSPs). These proteins are cytoprotective; thus, they make body cells more resilient to various microbes and toxins. Science has successfully identified may such proteins.
These proteins seem to have a dual role, protect from the external threat like a viral attack by making it more difficult for them to penetrate cells. Secondly, these proteins help protect body cells from higher than average body temperature. HSPs also improve stress tolerance.
Science has identified that all HSPs belong to four classes, based on their molecular weight. Science now knows that each type of HSPs has tens, if not hundreds of different proteins.
The prolonged external attack requires a more systematic defense approach, and it seems that the body’s way of initiating such a response is through the activation of certain genes. Many specific genes remain comparatively inactive during the normal body temperature. However, if the body temperature rises, it activates the so-called heat shock genes (HSG).
Thus, even a small rise in the body’s temperature sends an important message to genes present in all the cells. Once activated, these heat shock genes start producing vital proteins to protect the body. These genes cause a wide variety of changes; it is like switching to emergency mode and thus changing all the priorities. HSG ensures that cells try their best to defend and spend less energy on not so relevant tasks.
These newly active genes in response to heat may instruct cells to boost the production of antioxidants like Cu/Zn superoxide dismutase, and much more.
3. Induction of heat shock proteins (HSPs) in pathogens – helping to unmask invaders
Quite like various human body cells are required to produce HSPs, to strengthen the resistance power of the body cells, attacking pathogens are also needed to produce HSPs to protect themselves from elevated body temperature.
In air combat, enemy planes may silently sneak into the territory by switching off their radars and other equipment. But once inside the combat zone and threatened, they must activate all their combat systems. This makes it easy to intercept them. It is precisely what happens with microbes; high body temperature forces them to start their defensive responses to protect – by doing so, they become more resistant to immunity, but at the same time, easier to detect, and thus vulnerable.
Production of HSPs by pathogens makes them more readily identifiable by the range of immune mechanisms. Just take an example of E. coli, which starts producing lots of HSPs in response to higher intestinal temperature, but this immediately alerts the local population of macrophages. And quite like an advanced combat plane, macrophages launch multiple attacks towards the enemy in the form of interleukin, tumor necrosis factor, and much more. These compounds can kill the invading microbes.
Additionally, macrophages release chemical signals (in response to HSPs) for other cells to start collecting at the site. This results in the local inflammatory response. In military analogy, localized inflammation is comparable to the battlefield.
Researchers think that HSPs from pathogens serves as one of the early signals, helping to alert host defenses.
Localization of inflammatory responses in the body helps prevent the possibility of broader damage to the body of host organisms. Since the human immune cells release chemicals that not only kill pathogens but may also harm the cells of the body. And it seems that fever plays its role in localizing the inflammation to the area where it is needed most.
4. Immunomodulatory effect of high temperature
Another way in which it helps is through much broader immunomodulatory action. Fever is almost always an indication of widespread systemic infection. It means that disease is no more located to some location and has spread, posing a risk to the whole organism. Thus, the fever serves as a global alarm bell.
Fever causes widespread changes in the immune system, its strategy to cope with infection. It is like an order for mobilizing reserves. Therefore, it increases the activity of all the cells, of phagocytosis (ability to eat pathogens), chemotaxis (chemical signaling), the bactericidal and viricidal ability of the body.
There is some indication that higher body temperature boosts the production of various immune cells.
However, it is worth noticing that the various activities of immune cells may get suppressed if the body temperature rises above 41 degrees Celsius. Thus, an extremely high temperature is counterproductive and even damaging. Though such an increase in body temperature is not common, if it happens, it requires management through medications or applying cold packs.
Researchers think that an uncontrolled rise in body temperature happens due to the dysfunction of the body’s thermostat located in the hypothalamus (a part of the brain that senses and controls the body’s temperature). In most cases, a fever is a well calculated and controlled response, but in rare instances, the hypothalamus fails to keep the check and thus do more damage than good.
To conclude, a fever is an ancient phenomenon that is used by many species to fight intruders, or infections, and is quite effective in neutralizing viruses. Though it causes enormous discomfort and has a high metabolic cost, it is an essential defensive reaction that must not be weakened through the irrational use of antipyretic drugs.
The use of antipyretic medications should be avoided in the early stages of seasonal flu, common cold, especially if the temperature is below 40 degrees Celsius. The human body can more efficiently eradicate viruses commonly involved in seasonal illnesses like coronavirus and rhinovirus.
The use of medications to suppress fever is only justified when the extremely high temperature continues for a prolonged time and thus becoming a health threat in itself.