How do pyrogens induce fever through prostaglandin synthesis?

• A. Pyrogens suppress hypothalamic COX enzymes reducing PGE2
• B. Pyrogens stimulate sympathetic nerves directly raising body temperature
• C. Pyrogens stimulate hypothalamic COX enzymes increasing PGE2 synthesis, raising the set point
• D. Pyrogens decrease metabolic rate to conserve heat

Answer: (C)

Fever from pyrogens arises when they raise the hypothalamic temperature set point by increasing prostaglandin E2 synthesis. Pyrogens—like bacterial components or immune cytokines such as IL-1, IL-6, and TNF—activate COX enzymes in the hypothalamus, promoting the production of PGE2 from arachidonic acid. PGE2 then acts on receptors in the hypothalamus to raise the set point. To reach this higher set point, the body generates heat and reduces heat loss (shivering and vasoconstriction), producing fever. Inhibiting COX enzymes lowers fever by decreasing PGE2 synthesis, thereby lowering the set point. The other options don’t fit because fever is not caused by suppression of COX, direct sympathetic stimulation, or a reduced metabolic rate.