Which arachidonic acid metabolite is responsible for causing fever by acting on the hypothalamic thermoregulatory center, and what is its precursor mediator?
- A Leukotriene B4 derived from 5-LOX pathway; precursor: IL-6
- B Thromboxane A2 from platelets acting on hypothalamic TPR receptors; precursor: IL-8
- C PGE2 synthesized by COX-2 in vascular endothelium and brain; precursor cytokine: IL-1, TNF, or IL-6 ✓
- D Lipoxin A4 as an anti-inflammatory resolution mediator stimulating the hypothalamus
Correct answer: C. PGE2 synthesized by COX-2 in vascular endothelium and brain; precursor cytokine: IL-1, TNF, or IL-6
Explanation
Fever is mediated by PGE2 acting on EP3 receptors in the hypothalamic preoptic area, elevating the set point for body temperature via cAMP. PGE2 is produced by COX-2 in perivascular endothelial cells of the hypothalamus in response to endogenous pyrogens IL-1β, TNF-α, and IL-6 (themselves induced by LPS, immune complexes, and other stimuli). NSAIDs reduce fever by inhibiting COX-2 and thus blocking PGE2 synthesis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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