How do mice get fever? - briefly
Mice develop fever when pyrogenic stimuli—such as bacterial endotoxin, viral infection, or inflammatory cytokines—activate immune cells that release interleukin‑1, interleukin‑6, and tumor necrosis factor‑α. These mediators act on the hypothalamus to raise the thermoregulatory set point, resulting in an elevated core temperature.
How do mice get fever? - in detail
Mice develop an elevated body temperature through a cascade that begins with the detection of pyrogenic signals. When microorganisms, bacterial endotoxins, or inflammatory molecules enter the bloodstream, immune cells such as macrophages and dendritic cells recognize them via pattern‑recognition receptors. This recognition triggers the release of pro‑inflammatory cytokines—primarily interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), and interleukin‑6 (IL‑6).
These cytokines act on the organ that regulates thermal set‑point, the hypothalamus. They stimulate the production of prostaglandin E₂ (PGE₂) by inducing cyclooxygenase‑2 (COX‑2) in endothelial cells of the brain vasculature. PGE₂ binds to EP3 receptors on hypothalamic neurons, shifting the thermoregulatory set‑point upward. The nervous system then initiates heat‑conserving and heat‑generating responses: peripheral vasoconstriction reduces heat loss, shivering increases muscle activity, and metabolic rate rises through activation of brown adipose tissue.
The fever response in mice can be experimentally induced by several methods:
- Intraperitoneal injection of lipopolysaccharide (LPS) from Gram‑negative bacteria.
- Administration of bacterial toxins such as streptococcal pyrogenic exotoxin.
- Viral infection models (e.g., influenza, murine hepatitis virus) that elicit systemic cytokine release.
- Sterile inflammation induced by agents like carrageenan or zymosan.
Physiological measurements typically involve rectal thermometry or implanted telemetry probes, which record core temperature changes in real time. The magnitude and duration of the temperature rise depend on the dose of the pyrogenic stimulus, the mouse strain, age, and sex, as well as the presence of genetic modifications affecting cytokine signaling pathways.
Resolution of the febrile episode occurs when anti‑inflammatory mediators—IL‑10, transforming growth factor‑β, and glucocorticoids—suppress cytokine production and COX‑2 expression, leading to a decline in PGE₂ levels. The hypothalamic set‑point returns to baseline, and thermoregulatory mechanisms shift toward heat dissipation (vasodilation, sweating analogues, reduced shivering).
Understanding the detailed pathway from pathogen detection to hypothalamic temperature adjustment provides a foundation for interpreting fever as a measurable indicator of immune activation in murine research.