Brain Control of Temperature

Fever: A regulated elevation of core temperature resulting from infection or disease.
- Caused by circulating cytokines called pyrogens (low molecular weight polypeptides produced by immune cells).
- Hypothalamus actively regulates core temperature to an elevated set point ( $T_{set}$ ).
Hyperthermia of Exercise: Heat production temporarily exceeds heat dissipation.

Exercise Hyperthermia:
- Rate of heat production increases more than heat dissipation causing net heat storage.
- Temperature set point ( $T_{set}$ ) remains unchanged.
- Error signal gradually increases.
Fever:
- Temperature set point ( $T_{set}$ ) suddenly increases to a value higher than normal.
- The body interprets normal temperature as being lower than the new $T_{set}$ .
- Heat loss decreases, or heat production increases until core temperature reaches the new regulated level.
- Error signal is initially large, becoming smaller as fever develops.
- Core temperature remains elevated until the signal for fever subsides, and $T_{set}$ returns to normal.

Macrophages and T lymphocytes release cytokines in response to infections and inflammatory stimuli.
Cytokines: Messenger molecules of the immune system; diverse proteins involved in host defense.
- Immune response to foreign substances.
  - Stimulation of T lymphocyte proliferation, natural killer cells, and antibody production.
- Acute phase response to foreign substances.
  - Diffuse collection of nonspecific host reactions to infection or trauma.
- Act as endogenous pyrogens.

No single cytokine fully mimics the temperature increase during fever.
Interleukin 1 beta interacts with endothelial cells in the Organum Vasculosum Laminae Terminalis (OVLT).
- OVLT: Highly vascular tissue in the wall of the third ventricle above the optic chiasm.
Interleukin 1 beta triggers endothelial cells within the OVLT to release prostaglandin E2 (PGE2).
PGE2 diffuses into the hypothalamus and elevates $T_{set}$ , initiating the febrile response.