Editing Fever (section)

====Endogenous====
Endogenous pyrogens are [[cytokine]]s released from [[monocyte]]s (which are part of the [[immune system]]).<ref>{{cite book |title=Veterinary Medicine |date=2017-01-01 |publisher=W.B. Saunders |isbn=978-0-7020-5246-0 |editor-last=Constable |editor-first=Peter D. |edition=11th |pages=43–112 |chapter=4 – General Systemic States |doi=10.1016/b978-0-7020-5246-0.00004-8 |editor2-last=Hinchcliff |editor2-first=Kenneth W. |editor3-last=Done |editor3-first=Stanley H. |editor4-last=Grünberg |editor4-first=Walter |name-list-style=vanc |s2cid=214758182}}</ref> In general, they stimulate chemical responses, often in the presence of an [[antigen]], leading to a fever. Whilst they can be a product of external factors like exogenous pyrogens, they can also be induced by internal factors like [[damage associated molecular pattern]]s such as cases like [[rheumatoid arthritis]] or lupus.<ref>{{cite journal |vauthors=Dinarello CA |date=2015-03-31 |title=The history of fever, leukocytic pyrogen and interleukin-1 |journal=Temperature |volume=2 |issue=1 |pages=8–16 |doi=10.1080/23328940.2015.1017086 |pmc=4843879 |pmid=27226996}}</ref>

Major endogenous pyrogens are [[interleukin 1]] (α and β)<ref name="boron-58">{{cite book |author=Stitt, John |url=https://books.google.com/books?id=unBlQgAACAAJ |title=Medical Physiology: A Cellular and Molecular Approach |publisher=Elsevier Saunders |year=2008 |isbn=9781416031154 |veditors=Boron WF, Boulpaep, EL |edition=2nd |location=Philadelphia |chapter=Chapter 59: Regulation of Body Temperature |access-date=2 April 2020 |url-access=subscription}}</ref>{{rp|1237–1248}} and [[interleukin 6]] (IL-6).<ref>{{Cite book |last=Murphy, Kenneth (Kenneth M.) |title=Janeway's immunobiology |others=Weaver, Casey |year=2017 |isbn=978-0-8153-4505-3 |edition=9th |location=New York |pages=118–119 |oclc=933586700}}</ref> Minor endogenous pyrogens include [[interleukin-8]], [[Lymphotoxin alpha|tumor necrosis factor-β]], [[macrophage inflammatory protein]]-α and macrophage inflammatory protein-β as well as [[interferon-α]], [[IFN-β|interferon-β]], and [[Interferon-gamma|interferon-γ]].<ref name="boron-58" />{{rp|1237–1248}} [[Tumor necrosis factor-α]] (TNF) also acts as a pyrogen, mediated by [[interleukin 1]] (IL-1) release.<ref>{{cite journal |vauthors=Stefferl A, Hopkins SJ, Rothwell NJ, Luheshi GN |date=August 1996 |title=The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha and interactions with IL-beta in the rat |journal=British Journal of Pharmacology |volume=118 |issue=8 |pages=1919–1924 |doi=10.1111/j.1476-5381.1996.tb15625.x |pmc=1909906 |pmid=8864524}}</ref> These cytokine factors are released into general circulation, where they migrate to the brain's [[circumventricular organ]]s where they are more easily absorbed than in areas protected by the [[blood–brain barrier]].<ref>{{Citation |last1=Kennedy |first1=Rachel H. |title=Neuroimmune Signaling: Cytokines and the CNS |date=2016 |work=Neuroscience in the 21st Century |pages=1–41 |editor-last=Pfaff |editor-first=Donald W. |url=https://doi.org/10.1007/978-1-4614-6434-1_174-1 |access-date=2024-06-26 |place=New York |publisher=Springer |doi=10.1007/978-1-4614-6434-1_174-1 |isbn=978-1-4614-6434-1 |last2=Silver |first2=Rae |editor2-last=Volkow |editor2-first=Nora D.}}</ref> The cytokines then bind to [[endothelium|endothelial receptor]]s on vessel walls to receptors on [[microglial cell]]s, resulting in activation of the [[arachidonic acid pathway]].<ref>{{Cite book |last=Eskilsson |first=Anna |title=Inflammatory Signaling Across the Blood-Brain Barrier and the Generation of Fever |date=2020 |publisher=Linköping University, Department of Biomedical and Clinical Sciences |isbn=978-91-7929-936-1 |location=Linköping}}</ref>

Of these, IL-1β, TNF, and IL-6 are able to raise the temperature setpoint of an organism and cause fever. These proteins produce a [[cyclooxygenase]] which induces the hypothalamic production of PGE2 which then stimulates the release of neurotransmitters such as [[cyclic adenosine monophosphate]] and increases body temperature.<ref>{{cite book |last1=Srinivasan |first1=Lakshmi |title=Fetal and Neonatal Physiology |last2=Harris |first2=Mary Catherine |last3=Kilpatrick |first3=Laurie E. |date=2017-01-01 |publisher=Elsevier |isbn=978-0-323-35214-7 |editor-last=Polin |editor-first=Richard A. |edition=5th |pages=1241–1254.e4 |chapter=128 – Cytokines and Inflammatory Response in the Fetus and Neonate |doi=10.1016/b978-0-323-35214-7.00128-1 |editor2-last=Abman |editor2-first=Steven H. |editor3-last=Rowitch |editor3-first=David H. |editor4-last=Benitz |editor4-first=William E. |name-list-style=vanc}}</ref>