TAILIEUCHUNG - Chapter 017. Fever and Hyperthermia (Part 4)

Chronology of events required for the induction of fever. AMP, adenosine 5'-monophosphate; IFN, interferon; IL, interleukin; PGE2, prostaglandin E2; TNF, tumor necrosis are four receptors for PGE2, and each signals the cell in different ways. Of the four receptors, the third (EP-3) is essential for fever: when the gene for this receptor is deleted in mice, no fever follows the injection of IL-1 or endotoxin. Deletion of the other PGE2 receptor genes leaves the fever mechanism intact. Although PGE2 is essential for fever, it is not a neurotransmitter. Rather, the release of PGE2 from the brain side of. | Chapter 017. Fever and Hyperthermia Part 4 Chronology of events required for the induction of fever. AMP adenosine 5 -monophosphate IFN interferon IL interleukin PGE2 prostaglandin E2 TNF tumor necrosis are four receptors for PGE2 and each signals the cell in different ways. Of the four receptors the third EP-3 is essential for fever when the gene for this receptor is deleted in mice no fever follows the injection of IL-1 or endotoxin. Deletion of the other PGE2 receptor genes leaves the fever mechanism intact. Although PGE2 is essential for fever it is not a neurotransmitter. Rather the release of PGE2 from the brain side of the hypothalamic endothelium triggers the PGE2 receptor on glial cells and this stimulation results in the rapid release of cyclic adenosine 5 -monophosphate cyclic AMP which is a neurotransmitter. As shown in Fig. 17-1 the release of cyclic AMP from the glial cells activates neuronal endings from the thermoregulatory center that extend into the area. The elevation of cyclic AMP is thought to account for changes in the hypothalamic set point either directly or indirectly by inducing the release of neurotransmitters . Distinct receptors for microbial products are located on the hypothalamic endothelium. These receptors are called Toll-like receptors and are similar in many ways to IL-1 receptors. The direct activation of Toll-like receptors also results in PGE2 production and fever. Production of Cytokines in the CNS Several viral diseases produce active infection in the brain. Glial and possibly neuronal cells synthesize IL-1 TNF and IL-6. CNTF is also synthesized by neural as well as neuronal cells. What role in the production of fever is played by these cytokines produced in the brain itself In experimental animals the concentrations of cytokine required to cause fever are several orders of magnitude lower with direct injection into the brain than with IV injection. Therefore CNS production of these cytokines apparently can .

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