Editing Fever (section)

===Hypothalamus===
Temperature is regulated in the [[hypothalamus]]. The trigger of a fever, called a pyrogen, results in the release of [[prostaglandin E2]] (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. There are four receptors in which PGE2 can bind (EP1-4), with a previous study showing the EP3 subtype is what mediates the fever response.<ref>{{cite journal |vauthors=Ushikubi F et al. |date=September 1998 |title=Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3 |journal=Nature |volume=395 |issue=6699 |pages=281–284 |bibcode=1998Natur.395..281U |doi=10.1038/26233 |pmid=9751056 |s2cid=4420632}}</ref> Hence, the hypothalamus can be seen as working like a [[thermostat]].<ref name="Harrisons20th" /> When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral [[vasoconstriction]] both reduces heat loss through the skin and causes the person to feel cold. [[Norepinephrine]] increases [[thermogenesis]] in [[brown adipose tissue]], and muscle contraction through shivering raises the [[Basal metabolic rate|metabolic rate]].<ref name="pmid25976513">{{cite journal |vauthors=Evans SS, Repasky EA, Fisher DT |date=June 2015 |title=Fever and the thermal regulation of immunity: the immune system feels the heat |journal=Nature Reviews. Immunology |volume=15 |issue=6 |pages=335–349 |doi=10.1038/nri3843 |pmc=4786079 |pmid=25976513}}</ref>

If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, the brain orchestrates heat effector mechanisms via the [[autonomic nervous system]] or primary motor center for shivering. These may be:<ref>{{Cite journal |last=Nakamura |first=Kazuhiro |date=November 2011 |title=Central circuitries for body temperature regulation and fever |url=https://www.physiology.org/doi/10.1152/ajpregu.00109.2011 |journal=American Journal of Physiology-Regulatory, Integrative and Comparative Physiology |language=en |volume=301 |issue=5 |pages=R1207–R1228 |doi=10.1152/ajpregu.00109.2011 |issn=0363-6119}}</ref><ref>{{Cite journal |last=Morrison |first=S.F. |last2=Nakamura |first2=K. |date=2019-02-10 |title=Central Mechanisms for Thermoregulation |url=https://www.annualreviews.org/doi/10.1146/annurev-physiol-020518-114546 |journal=Annual Review of Physiology |language=en |volume=81 |issue=1 |pages=285–308 |doi=10.1146/annurev-physiol-020518-114546 |issn=0066-4278}}</ref><ref>{{Cite journal |last=Nakamura |first=Kazuhiro |last2=Nakamura |first2=Yoshiko |last3=Kataoka |first3=Naoya |date=January 2022 |title=A hypothalamomedullary network for physiological responses to environmental stresses |url=https://www.nature.com/articles/s41583-021-00532-x |journal=Nature Reviews Neuroscience |language=en |volume=23 |issue=1 |pages=35–52 |doi=10.1038/s41583-021-00532-x |issn=1471-003X}}</ref>
* Increased heat production by increased [[muscle tone]], [[shivering]] (muscle movements to produce heat) and release of hormones like [[epinephrine]]; and
* Prevention of heat loss, e.g., through [[vasoconstriction]].
When the hypothalamic set point moves back to baseline—either spontaneously or via medication—normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.{{citation needed|date=April 2020}}

This contrasts with [[hyperthermia]], in which the normal setting remains, and the body overheats through undesirable retention of excess heat or over-production of heat. Hyperthermia is usually the result of an excessively hot environment ([[heat stroke]]) or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to [[anti-pyretic]] medications.<ref name="Harrisons20th" />{{verify source|date=April 2020}}

In infants, the autonomic nervous system may also activate [[brown adipose tissue]] to produce heat (non-shivering thermogenesis).<ref>{{Cite journal |last1=Nowack |first1=Julia |last2=Giroud |first2=Sylvain |last3=Arnold |first3=Walter |last4=Ruf |first4=Thomas |date=2017-11-09 |title=Muscle Non-shivering Thermogenesis and Its Role in the Evolution of Endothermy |journal=Frontiers in Physiology |volume=8 |page=889 |doi=10.3389/fphys.2017.00889 |issn=1664-042X |pmc=5684175 |pmid=29170642 |doi-access=free}}</ref>

Increased heart rate and vasoconstriction contribute to increased [[blood pressure]] in fever.<ref>{{Cite journal |last=Deussen |first=A. |date=September 2007 |title=[Hyperthermia and hypothermia. Effects on the cardiovascular system] |url=https://pubmed.ncbi.nlm.nih.gov/17554514/ |journal=Der Anaesthesist |volume=56 |issue=9 |pages=907–911 |doi=10.1007/s00101-007-1219-4 |issn=0003-2417 |pmid=17554514}}</ref>