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I am currently reading "The Fundamentals of Anatomy Physiology" 10th edition, and have found it an incredibly interesting book. I have just been reading about the lymphatic system, and the various Leukocytes and their roles. When it mentioned fever as an immune response, I was familiar with the concept: Bacteria and viruses operate very nicely at our usual body temperature, but not so well at around 39 degrees Celsius.

What I wasn't aware of was "For each 1 degree Celsius rise in body temperature, metabolic rate increases by 10 percent. Cells can move faster, and enzymatic reactions take place quicker." (Quoted from page 828 of that book).

Now that seems like a massive benefit (though I believe you could only really push 1 or 2 degrees before you start getting into dangerous territory), but I notice that fever is not present in all illnesses. Inflammation seems to induce fever through the wounded area, which makes sense.

So now for my question: Could it be beneficial to artificially induce fever in a person who has an illness if they are not already experiencing fever? I believe a few things would need to be considered (more than likely a lot more than I can think to list):

  • Increased metabolic activity would surely need a higher energy intake would it not?
  • Are there cells that are actually going to suffer from the temperature increase?
  • I'm assuming this would actually be a rather poor technique to deal with cancer as from my currently limited knowledge, it is simply a cell that is producing abnormal proteins. If this is the case, the metabolic increase would likely apply to these abnormal cells, resulting in faster proliferation. Are there other such cells/infections that will benefit from temperature increase?

Finally, what are possible downsides of long term fever if energy intake is sufficient to maintain an increased metabolic rate at these higher temperatures?

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Could it be beneficial to artificially induce fever in a person who has an illness if they are not already experiencing fever?

No, not really. Pretty much the only use of hyperthermia in medicine is in the treatment of cancer. If you google "use of hyperthermia in medical treatment", you'll likely only find two kinds of hits: those for cancer treatment and those for malignant hyperthermia (a side effect of some psychotropic drugs.) The hyperthermia used to kill resistant cancer cells is high enough to destroy proteins (~113°-114°) and very localized; your entire body raised to this temperature would result in death very quickly. Lower (i.e. physiological) levers of "hyperthermia" (or hyperpyrexia) would not kill the cells.

At the turn of the century, there were many who believed in the therapeutic use of hyperthermia in the form of hot baths, hot springs, and even injection of infectious agents to produce fever(!), but the practice has fallen into disuse, probably because there were no studies which supported it.

However, hyperthermia isn't good for you; it is something to treat seriously. When the cause isn't known, the efforts used to treat it can amount to many unnecessary tests and treatments (as seen in the accident victim in the fourth reference. When it's present in a moderate amount, it can still be dangerous:

When fever occurs, many physiological stresses take place. Some of these include increased oxygen consumption as a response to increased cell metabolism, increased heart rate, increased cardiac output, increased leukocyte count, and an increased level of C-reactive protein. Oxygen consumption increases by 13% for every 1°C increase in body temperature, provided no shivering occurs. If shivering is present, oxygen consumption may increase by 100% to 200%. Some cytokines released during fever states also induce physiological stress. These cytokines can trigger accelerated muscle catabolism by causing weight loss, loss of strength, and negative nitrogen balance. Physiological stress can be manifested by decreased mental acuity, delirium, and seizures, which are more frequent in children.

It is likely beneficial in the presence of infection:

Heat shock proteins are one of the more recently studied fever-responsive proteins. These proteins are produced during fever states and are critical for cellular survival during stress. Studies suggest that these proteins may have anti-inflammatory effects by decreasing the levels of proinflammatory cytokines. Fever also triggers other beneficial effects, including an increase in the phagocytic and bacteriocidal activity of neutrophils and enhanced cytotoxic effects of lymphocytes. Some bacteria become less virulent and grow slower at the higher temperatures associated with fever. Increased levels of C-reactive protein promote phagocytic adherence to invading organisms, modulate inflammations, and encourage tissue repair.

In the absence of infection, there is no benefit to systemic elevation of temperature. For the disadvantages of continued elevated metabolic rate, one need only look at hyperthyroidism to see the deleterious effects, the worst being cardiotoxicity, even in subclinical hyperthyroidism, as well as dementia, atrial fibrillation, ventricular hypertrophy, miscarriage, perinatal morbidity and mortality, decreased exercise tolerance, etc.

Years ago, one of the most common self-inflicted illnesses was hyperthyroidism - people taking thyroid hormone replacement unnecessarily - usually because of the weight loss that occurs with elevated metabolic states. Interestingly, efforts are underway to isolste and manufacture a thyroid-hormone like substance which will cause decreased weight without cardiotoxic effects.

Hyperthermia in Cancer Treatment
HYPERPYREXIA PRODUCED BY BATHS
ARTIFICIAL FEVER IN THE TREATMENT OF GONORRHEAL OPHTHALMIA
Thyrotoxicosis in a patient with multiple trauma
Metabolic Effects of Thyroid Hormone Derivatives

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    $\begingroup$ "At the turn of the century, there were many who believed in the therapeutic use of hyperthermia in the form of hot baths, hot springs, and even injection of infectious agents to produce fever(!), but the practice has fallen into disuse, probably because there were no studies which supported it." Not so. Julius Wagner-Jauregg won a Nobel Prize given for his studies on malaria pyrotherapy. This approach was discontinued because of the advent of antibiotics, not for lack of evidence! $\endgroup$
    – Corvus
    Commented Mar 31, 2015 at 2:46
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    $\begingroup$ Hyperthermia isn't used for malaria--rather, patients were deliberately infected with malaria to treat syphilis because malaria induces high fever. Whatever the intent of your post, the claim "no studies...supported it" is badly at odds with the fact that a Nobel Prize was given for precisely such studies and so this seemed a correction worth making if we care about the faculty accuracy of biology.SE. More generally, having read a hundred or so recent studies about the effects of endogenous or induced fever on infectious disease clearance, I think you are dismissing hyperthermia too quickly. $\endgroup$
    – Corvus
    Commented Mar 31, 2015 at 3:49
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    $\begingroup$ Once I get my head around the subject fully I'll be happy to do so. It's not an easy topic to synthesize because there are so many individual facts and study results out there, and so little by way of coherent explanation for the entirety of the phenomenon. The evidence seems overwhelming that fever hastens viral and bacterial clearance, but despite numerous conjectures there is no decisive explanation for the causative mechanism by which it does this. $\endgroup$
    – Corvus
    Commented Mar 31, 2015 at 4:14
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    $\begingroup$ This has really helped me get a direction as to what I need to look at, so thank you very much for this! I shall look at all of the references as time permits and see what they say. @Corvus If you have some stuff you would like to add in to an answer with some other references and ideas, that would be good. The more information I have that indicates relevant areas, the better! Seems like hyperthermia has a huge affect on parts of the body, as I expected. It seems like the answer is something like: Yes it is good in some cases with side effects, and no in others. $\endgroup$
    – Stevo
    Commented Mar 31, 2015 at 4:25
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    $\begingroup$ @Corvus... You seem to hold the Nobel Prize up to some biblical standard... How about António Egas Moniz developer of the Prefrontal Lobotomy and 1949 Nobel Prize winner in Medicine in Physiology for "for his discovery of the therapeutic value of leucotomy in certain psychoses"? Wagner-Jauregg's treatments, while effective and a keystone in the development of neuropharmacological treats, were at best ethically questionable. Also he got lucky in that the cause of the Dementia was bacterial in nature. His research was looking to use fever as a cure for all forms of "insanity." $\endgroup$
    – AMR
    Commented Aug 28, 2015 at 5:17
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Actually, hyperthermia is a known treatment for a range of diseases, including cancer.

Induced hyperthermia can be whole-body as well as local/regional and is under investigation in multiple studies (for example).

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  • $\begingroup$ Those studies you linked to are quite interesting. I will look into some more recent studies and see what they have found. And thank you for referring to it as hyperthermia, it is a much more appropriate term! $\endgroup$
    – Stevo
    Commented Mar 27, 2015 at 23:00
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    $\begingroup$ This would be a much better answer if there was more than a yes/no, and a couple of links. $\endgroup$
    – anongoodnurse
    Commented Mar 28, 2015 at 0:31
  • $\begingroup$ @anongoodnurse I found the links fairly helpful, but they related primarily to cancer treatment (which still nicely addresses something that I had a misconception about in my question). Are there any other things you could recommend I look into to better understand the concept I described? $\endgroup$
    – Stevo
    Commented Mar 28, 2015 at 0:37
  • $\begingroup$ @Stevo - I'll look into this and post something more comprehensive and balanced tomorrow (if no one else does!) $\endgroup$
    – anongoodnurse
    Commented Mar 28, 2015 at 0:39
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    $\begingroup$ lol, why did you delete yours? I deleted mine because they are not relevant to most users. But if you insist: This is a poor answer, with an opinion and a couple of links. SE strives for better. Please read "how to answer" in the help section for guidance on how to answer questions. $\endgroup$
    – anongoodnurse
    Commented Mar 28, 2015 at 8:19
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In terms of bacteria and viruses within humans, the reason the bacteria and viruses function well at normal body temperature is because it's normal. If fever were a perpetual state, the bacteria and viruses would evolve to be fit at that fever state.

There is also reason to believe that one way aging occurs is through metabolism (https://www.sciencedaily.com/releases/2011/04/110427091949.htm). Thus, perpetual fever would likely reduce life span.

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