The hypothalamic thermostat set-point for body temperature is elevated during fever by which mediator acting directly on the anterior hypothalamus?

• A Interleukin-6 (IL-6) crossing the blood-brain barrier
• B TNF-alpha acting directly on anterior hypothalamic neurons
• C Prostaglandin E2 (PGE2), synthesized locally at the organum vasculosum of the lamina terminalis (OVLT) ✓
• D Substance P released from sensory neurons

Explanation

Circulating pyrogens (IL-1β, IL-6, TNF-α) stimulate cyclooxygenase-2 (COX-2) in cerebral vascular endothelium and at the circumventricular organ OVLT, producing PGE2. PGE2 acts on EP3 receptors on anterior hypothalamic neurons to elevate the thermostat set-point, triggering heat-conservation (vasoconstriction) and heat-generation (shivering) responses that raise body temperature to the new set-point. Antipyretics (aspirin, paracetamol) inhibit COX-2, reducing PGE2 and lowering the set-point.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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