Fever stimulators and inhibitors

Starting from the top left, infectious agents and/or microbial products, as well as cytokines and other inflammatory processes, induce macrophages, endothelial cells, and the reticuloendothelial system to produce and secrete pyrogenic cytokines into the circulation. These pyrogenic cytokines induce the synthesis of PGE2 in the hypothalamus. In addition, microbial toxins, acting as ligands to the TLRs in the hypothalamus, stimulate the synthesis of PGE2 by the hypothalamus. PGE2 raises the thermostatic set point in the hypothalamus to febrile levels. The vasomotor center sends signals for heat conservation (vasoconstriction) and heat production (shivering). Corticosteroids reduce the peripheral synthesis of pyrogenic cytokines, whereas antipyretics reduce PGE2 levels in the brain. Dantrolene directly inhibits heat production.