Preparatory Mindset

Fever is a physiological response, not a disease. Pyrogens (exogenous = bacterial toxins; endogenous = IL-1, IL-6, TNF) reset the hypothalamic set point via prostaglandin E2. Antipyretics work by inhibiting COX → ↓ PG synthesis. Know the difference between fever and hyperthermia (set point is normal in hyperthermia).

Core Concepts

• Fever = elevation of body temperature due to resetting of hypothalamic set point by pyrogens.


• Exogenous pyrogens: bacterial toxins, viruses.


• Endogenous pyrogens: IL-1, IL-6, TNF (produced by immune cells).


• These stimulate PGE₂ synthesis in hypothalamus → ↑ set point.


• Antipyretics (acetaminophen, NSAIDs) inhibit COX → ↓ PGE₂.


• Hyperthermia: set point is normal but temperature is elevated due to heat production > dissipation (heat stroke, malignant hyperthermia) — antipyretics DON'T work..

High-Yield Points

• Pyrogens: exogenous (LPS from bacteria) → endogenous (IL-1, IL-6, TNF) → hypothalamus → ↑ set point


• Antipyretics inhibit COX → ↓ PGE₂ synthesis


• Fever ≠ hyperthermia (set point normal in hyperthermia)


• Febrile seizures: most common in children 6 months to 5 years

Topic Summary

Fever is caused by pyrogens resetting the hypothalamic thermostat upward. Antipyretics (acetaminophen, NSAIDs) inhibit COX to reduce prostaglandin synthesis. Hyperthermia differs from fever because the set point remains normal.