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Allergy

To my understanding, an allergy is a hypersensitivity of the immune system causing a substance in the environment to be identified as pathogenic by the immune system while it is not pathogenic. During an allergic reaction, the immune system triggers histamine, which triggers an inflammatory response just as if the allergen was a pathogen. The resulting symptoms of an allergic response is similar to the symptoms of a cold but without fever.

Fever

To my understanding a fever is an increase in body temperature driven by the body through production of pyrogens, most often in response to a pathogen. This response might be adaptive for various reasons that I am not too interested in discussing here.

Question

According to NIH, an allergic response never causes a fever. Given that the fever is not directly caused by the pathogen but rather is caused by the body, why do allergies not cause fever?

The fact that allergies don't cause fever give me the weird impression that the immune system somewhat "understand" the allergen is not pathogenic otherwise the immune response would be the same in the case of an allergen or a pathogen.

Un-educated guess

Allergic responses implies the firing of IgE. IgE are typically involved in response to parasites such as helminths. Could it be that pathogens leading to an immune responses mediated via IgE never yield to fever. Why would it be the case?

Plasmodium falciparum (which causes malaria) is a pathogen who causes an immune response involving IgE (according to the wikipedia). Malaria's symptoms include high fever (according to Mayo Clinic). Now it would be possible that the pyrogen would be of external origin (not produced by the body but by the pathogen) or it is possible that several immunoglobulin are involved in response to P. falciparum. The same logic hold for Fasciola hepatica (an helminth; common liver fluke) who also causes fever and is who's infection lead to the firing of IgE.

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The short answer seems to be that fevers help combat microbes (a term I take herein to include viruses for brevity), which aren't a part of the threat addressed in an allergic reaction. While there's not a full consensus on which benefits, if any, a fever brings to the response to microbes, both humans and other warm-blooded vertebrates fare better with infections when a fever is present.

Fevers appear to mobilise leukocytes and enhance their phagocytosis while suppressing endotoxin effects (see Craven, R and Hirnle, C. (2006). Fundamentals of nursing: Human health and function. Fourth edition. p. 1044) and proliferate T cells (see Lewis, SM, Heitkemper, MM, and Dirksen, SR. (2007). Medical-surgical nursing: Assessment and management of clinical problems. sixth edition. p. 212), rather than mobilising basophils.

Higher temperatures are also more damaging to at least some pathogenic cells than the body's own, as they are typically smaller with higher relative surface area. Note this also explains why fevers wouldn't be as natural a response to such large parasites as helminths. (Even their cells, being eukaryotic, are comparable to human cells.) It is unsurprising that IgE would be a more specialised response, found only in mammals.

On the subject of malarial fever, for which the pathogen is relatively large because it is eukaryotic, there is ongoing research into both the mechanism and function of this fever. It seems to be Plasmodium itself that creates and presumably benefits from the fever, not the host. I'll discuss the evidence in a moment, but note this means the "endogenous fevers follow suspected small pathogens" hypothesis is unthreatened.

According to this 2013 paper, the timing of such ruptures may (I stress may; the paper discusses the uncertainty around a number of ideas about this) serve the function of controlling the time at which the immune response is most active, so the reproductive cycle is unaffected. According to this 2007 paper, the malarial parasite's hemozoin causes the disease's characteristic fever following erythrocyte rupture. The same paper mentions that the timing of the fever has been used as a diagnostic criterion for malaria, and the 1927 Nobel Prize for Medicine was awarded for the now discontinued treatment of syphilis with a malaria-induced fever.

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    $\begingroup$ By the same logic, the body doesn't need to "combat" peanuts, pollen, or cat hair with an inflammatory response, yet it does for people with allergies to those things. $\endgroup$
    – mgkrebbs
    Commented Apr 7, 2019 at 6:14
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    $\begingroup$ @mgkrebbs I'll admit the immune system has to be imperfect whatever explanation one advances, but I think the evidence suggests allergens are mischaracterised as poisons or toxins rather than as pathogenic microbes. $\endgroup$
    – J.G.
    Commented Apr 7, 2019 at 9:24
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    $\begingroup$ @J.G. I don't think this answer adds much beyond the background already contained in the question - can you provide some citations? $\endgroup$
    – Bryan Krause ♦
    Commented Apr 7, 2019 at 15:47
  • $\begingroup$ In light of the reference-seeking notice (whose posting I welcome), I've edited my answer to directly reference the relevant primary literature, although in some cases this is a book or a possibly paywalled link. $\endgroup$
    – J.G.
    Commented Apr 7, 2019 at 16:15
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    $\begingroup$ @BryanKrause Whether or not my answer "adds much beyond the background", I think any answer needs to see the real question to be not "Why do allergies that don't warrant fevers still happen?" but "Given that allergies are clearly a mistake, why aren't they the same kind of mistake they would be if they were feverish?" Adverse reactions to vaccines, which can be feverish, are the microbe-detecting mistake type. $\endgroup$
    – J.G.
    Commented Apr 7, 2019 at 16:15

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