Fever - Pyrogen Pathophysiology EXOGENOUS PYROGEN • Bacteria: Lipopolysaccharide components, peptidoglycans and muramyl peptide derivatives, Toxins • Virus: Double stranded RNA • Fungi: Mannan and glucan components Exogenous Pyrogen → Stimulate immune cells (neutrophils, monocytes/macrophages) → Synthesis of proinflammatory mediators (endogenous pyrogen) TNF, IL-1, IFN, IL-6 ENDOGENOUS PYROGEN - Transport to brain vasculature via: • Active transport across blood-brain barrier • Passive transport through fenestrated capillaries in the circumventricular organs CNS - Endogenous Pyrogen → Induce synthesis of Prostaglandins (PGE2) → PGE2 stimulates cAMP in the hypothalamus → Elevates thermoregulatory set point → Heat conservation, Heat production → Fever #Fever #Pathophysiology #Pyrogen
