In the hypothalamic thermoregulatory system, the pre-optic anterior hypothalamic area (POAH) functions as the 'thermostat'. During fever induced by IL-1, the mechanism involves:

• A Direct inhibition of POAH neurons by IL-1 released from macrophages
• B TNF-alpha directly activating hypothalamic noradrenergic neurons
• C IL-1 crossing the blood-brain barrier and activating fever directly
• D PGE2 acting on EP3 receptors in the POAH, resetting the thermal set-point upwards ✓

Explanation

Exogenous pyrogens (bacteria, toxins) and endogenous cytokines (IL-1, IL-6, TNF-alpha) stimulate arachidonic acid metabolism in hypothalamic vascular endothelium and perivascular microglia, generating prostaglandin E2 (PGE2). PGE2 acts on EP3 (and EP1) receptors on warm-sensitive neurons in the POAH, inhibiting them and resetting the thermoregulatory set-point to a higher temperature. The body then activates heat-conservation and heat-generation mechanisms (vasoconstriction, shivering) to achieve the new set-point.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.