During fever, which thermoregulatory response is most responsible for the sensation of feeling cold (chills) even when core body temperature is rising?

• A Peripheral vasodilation dissipates heat and lowers skin temperature
• B Pyrogens directly activate peripheral cold receptors in skin
• C The hypothalamic set-point has been raised above current body temperature, causing the thermoregulatory center to activate heat-conserving mechanisms ✓
• D Sweating is suppressed causing heat retention and a perceived cold sensation

Explanation

During fever, IL-1, IL-6, TNF-α, and prostaglandin E2 (via cyclooxygenase in the preoptic area) raise the hypothalamic set-point. When the set-point exceeds actual core temperature, the preoptic-anterior hypothalamus activates heat-generating and heat-conserving mechanisms — shivering, cutaneous vasoconstriction, and piloerection — even as core temperature rises toward the new set-point. The individual experiences chills because the brain 'perceives' the body as too cold relative to the new elevated set-point.

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

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