{
  "id": "fever",
  "title": "Fever",
  "lang": "en",
  "source_lang": "en",
  "summary": "Fever is an elevation of core body temperature above its regulated set point, usually triggered by infection or inflammation through prostaglandin E2 signaling in the hypothalamus.",
  "category": "health",
  "subcategory": "diseases",
  "type": "concept",
  "aliases": [
    "Pyrexia",
    "febrile response"
  ],
  "generated_at": "2026-10-09",
  "model": "pro/claude-haiku-5-5",
  "url": "https://aiwiki.page/en/fever/",
  "translations": {
    "zh-Hans": {
      "url": "https://aiwiki.page/zh/fever/",
      "json": "https://aiwiki.page/zh/fever.json"
    }
  },
  "sections": [
    {
      "heading": "",
      "text": "Fever, or pyrexia, is an elevation of body temperature above the normal range that results from a raised set point of the body's thermoregulatory system. It is a complex physiological response to disease, most often to infection, and is mediated largely by immune signaling molecules that act on the hypothalamus. Although fever is a symptom rather than a disease in itself, it is one of the most common reasons people seek medical care."
    },
    {
      "heading": "Definition and thresholds",
      "text": "Fever has no single universally fixed definition. The International Union of Physiological Sciences describes it as a state of elevated core temperature that is often, but not necessarily, part of the defensive response of a multicellular host to invading microorganisms or other material recognized as pathogenic or alien. Clinically, it is usually defined as a pyrogen-mediated rise in body temperature above the normal range, and the operational cutoff is what most often appears in practice.\n\nCommonly used thresholds vary by measurement site. Oral readings of 38 °C or higher and rectal readings of about 38.3 °C or higher are widely cited. Some guidance for adults defines elevated oral temperature as 37.8 °C or more at any time after early morning, or a value higher than the person's own usual reading. Because normal body temperature varies over the day, with its lowest point in early morning and its highest in late afternoon or evening, a moderate evening reading may not be pathological.\n\nGuidelines for infants and young children differ. The American Academy of Pediatrics and related European guidance have traditionally used a fixed threshold of 38.0 °C at all ages, with rectal measurement recommended in children under three. Newer studies argue that the upper limit of normal varies with age, especially in early infancy, and that a fixed cutoff may need revision. The UK National Institute for Health and Care Excellence also treats infants under three months with a temperature of 38 °C or higher as a high-risk group for serious illness.\n\nPatients often use the word loosely to describe feeling warm, cold, or sweaty without having measured their temperature. Clinicians therefore distinguish measured fever from subjective feverishness."
    },
    {
      "heading": "Normal temperature regulation",
      "text": "Core body temperature is maintained by a balance between heat production, mainly in the liver and skeletal muscle, and heat loss from the skin and periphery. The hypothalamus acts as the central thermostat and keeps core temperature near a set point, commonly cited as between 37 and 38 °C. Heat is lost through evaporation (sweating), radiation, convection, and conduction, and heat is conserved through peripheral vasoconstriction. Ordinary daily fluctuation of about half a degree or more arises from sleep and wake cycles, metabolism, hormones, and activity."
    },
    {
      "heading": "Mechanism",
      "text": "Fever occurs when the hypothalamic set point is raised. The usual sequence begins with a pyrogen, a substance that induces fever. Exogenous pyrogens include components of microorganisms, such as lipopolysaccharide from the cell walls of Gram-negative bacteria. These stimulate immune cells, particularly macrophages, to release endogenous pyrogens, which are cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha.\n\nThese cytokines travel through the bloodstream to the brain's preoptic and anterior hypothalamic region. There they act on the vascular endothelium of the blood–brain barrier and stimulate production of prostaglandin E2 (PGE2). PGE2 is considered the principal final mediator of fever in humans. It binds to EP3 receptors in the preoptic hypothalamus, raising the thermostatic set point. The body then generates heat through shivering and increased metabolism and conserves heat through vasoconstriction, until the temperature of the blood bathing the hypothalamus matches the new set point. This explains why a person often feels chilled while the temperature is rising and feels warm once the new level is reached.\n\nExperimental work has refined this picture. Studies in mice have shown that PGE2 administered directly into the brain produces fever, and that the lipid pathways generating PGE2 in the hypothalamus are essential for the febrile response. Some questions remain open, including exactly how peripheral pyrogens signal across the blood–brain barrier, and how nutritional status and ambient temperature modify the response.\n\nFever is distinct from hyperthermia, an elevated body temperature not caused by a change in the set point, as in heat stroke or excessive exercise. In hyperthermia the regulatory system is overwhelmed, whereas in fever it is operating at a raised setting. The distinction matters for treatment, because antipyretic drugs that reduce the PGE2 pathway are generally ineffective against hyperthermia."
    },
    {
      "heading": "Causes",
      "text": "Fever is most commonly associated with bacterial and viral infections. It also accompanies non-infectious conditions, including immune-mediated and inflammatory diseases such as inflammatory disorders, adverse drug reactions, and some malignancies. Fever of unknown origin is a clinical category used when a fever persists without a diagnosis after standard investigation; one common definition requires temperatures above 38.3 °C on several occasions over at least three weeks."
    },
    {
      "heading": "Biological function",
      "text": "Fever is considered an adaptive part of the immune system's defense. Higher temperatures are thought to slow the replication of some microorganisms and to enhance several immune activities, including the function of certain immune cells. Experimental and clinical evidence supports a protective role in some infections, although the magnitude of benefit varies by pathogen and context. Most acute infections produce modest core temperature elevations, roughly 38 to 40 °C, which healthy adults tolerate well."
    },
    {
      "heading": "Clinical assessment and management",
      "text": "Fever is a sign that prompts diagnosis rather than a diagnosis in itself. Clinicians consider the patient's age, the height and duration of the fever, associated symptoms, and any signs of serious illness. Patients with acute fever should be promptly screened for sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection. Investigations depend on the suspected source and may include laboratory tests, cultures, and imaging.\n\nMany fevers do not require treatment, and the typical goal of antipyretic medicines is symptom relief rather than shortening the illness. Common antipyretics such as aspirin and other non-steroidal anti-inflammatory drugs inhibit cyclooxygenase enzymes and reduce PGE2 synthesis, while paracetamol (acetaminophen) acts through a related but less fully understood central mechanism. Physical cooling methods have limited effect on the set point. Fever in infants, in people with weakened immunity, or with signs of serious illness warrants prompt medical evaluation."
    },
    {
      "heading": "Significance and debate",
      "text": "Fever has been recognized as a sign of illness since ancient times, and its interpretation has changed with advances in pathology and pharmacology. Current debate centers on the appropriate threshold for children, on when to use antipyretics, and on whether suppressing fever affects outcomes in infections. Studies have reported mixed results, and guidance continues to evolve."
    }
  ],
  "links": [
    "bacteria",
    "macrophage",
    "infectious-disease",
    "inflammation",
    "immune-system",
    "sepsis",
    "pathology",
    "pharmacology"
  ],
  "sources": [
    {
      "title": "Threshold for defining fever varies with age, especially in children: A multi‐site diagnostic accuracy study - PMC",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8363342/"
    },
    {
      "title": "Fever - Physiopedia",
      "url": "https://www.physio-pedia.com/Fever"
    },
    {
      "title": "Fever - Infectious Disease - Merck Manual Professional Edition",
      "url": "https://www.merckmanuals.com/professional/infectious-diseases/biology-of-infectious-disease/fever"
    },
    {
      "title": "Fever",
      "url": "https://link.springer.com/chapter/10.1007/978-3-030-11775-7_10"
    },
    {
      "title": "Pathogenesis of Fever - PMC - NIH",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/"
    },
    {
      "title": "20.1F: Fever - Medicine LibreTexts",
      "url": "https://med.libretexts.org/Bookshelves/Anatomy_and_Physiology/Anatomy_and_Physiology_(Boundless)/20:_Immune_System/20.1:_Innate_Immunity/20.1F:_Fever"
    },
    {
      "title": "Fever",
      "url": "https://www.vhtc.org/2025/12/fever-causes-evaluation-management.html"
    },
    {
      "title": "Fever: Links with an ancient receptor: Current Biology",
      "url": "https://www.cell.com/current-biology/fulltext/S0960-9822(02)00013-1"
    },
    {
      "title": "Neural Mechanisms of Inflammation-Induced Fever",
      "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047205/"
    },
    {
      "title": "Prostaglandin E2 in the pathogenesis of fever. An update - PubMed",
      "url": "https://pubmed.ncbi.nlm.nih.gov/9917867"
    },
    {
      "title": "Fever - ScienceDirect",
      "url": "https://www.sciencedirect.com/science/article/abs/pii/S1357303908003101"
    },
    {
      "title": "Endogenous Pyrogen - an overview",
      "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/endogenous-pyrogen"
    },
    {
      "title": "Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2",
      "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511515/"
    },
    {
      "title": "17.1F: Fever - Medicine LibreTexts",
      "url": "https://med.libretexts.org/Courses/James_Madison_University/A_and_P_for_STEM_Educators/17:_Immune_System/17.01:_Innate_Immunity/17.1F:_Fever"
    },
    {
      "title": "A Clinical Overview Understanding of Fever ...",
      "url": "https://wjarr.com/sites/default/files/fulltext_pdf/WJARR-2025-2206.pdf"
    }
  ],
  "license": "https://creativecommons.org/licenses/by/4.0/"
}