1. Fever Fever describes an elevation in body temperature that results from a cytokine-induced increase in the set point of the thermostatic center in the hypothalamus.

2. Mechanism Pyrogenic activator microorganisms, their products and parasites (exogenous pyrogen) viruses, bacteria, mycobacteria, fungi, and parasites non-microbial factors antigen-antibody compound, alkaloids

3. Endogenous pyrogen (EP) Fever activators induce host cells to produce fever-producing substances called endogenous pyrogens. Cytokines: IL-1, IL-6, TNF- α, IFN Monocytes, endothelial cells, lymphocytes, fibroblasts

4. Routes of peripheral pyrogenic signals into thermostatic center Humoral mechanisms through OVLT circulatory EP local EP activated monocytes pyrogenic activators Neural mechanism peripheral nerve and vagal nerve

5. Increased set point of thermostatic center PGE2 CRH Na + /Ca 2+ cAMP Negative regulatory mediators AVP(ADH), α-MSH, lipocortin-1

6. Stages The fervescence period shivering, oxidation of brown adipose tissue vasoconstriction The persistent febrile period metabolic rate↑ vasodilation The defervescence period vasodilation, sweating

7. Alterations of metabolism and function Metabolism metabolic rate will increase 13% while 1 ℃ elevation in body T gulcose, adipose, protein Central nervous system headache, irritability, delirium, hallucination, febrile convulsion (children)

8. Cardiovascular system (SN ↑, blood T ↑) every 1 ℃ rise in body T will lead to a 18 bpm increase in heart beats. Respiratory system ( blood T ↑→respiratory center) hyperventilation respiratory alkalosis Digestive system be suppressed(SN↑,PG) anorexia, abdominal distension, constipation, vomiting Immune system be activated APP(complements), lymphocyte activation

9. Pathophysiological basis of prevention and treatment Treatment of the primary disease Anti-pyretic medications drugs (salicylate) (>40 ℃ except children, pregnant women and patients with severe heart disease) Fluid and carbohydrates