Neural Mechanisms of Inflammation-Induced Fever

Abstract

Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E2 synthesis in these cells. The evidence for a role for other signaling routes for fever, such as signaling via circumventricular organs and peripheral nerves, as well as transfer into the brain of peripherally synthesized prostaglandin E2 are yet far from conclusive. We also review the efferent limb of the pyrogenic pathways. We conclude that it is well established that prostaglandin E2 binding in the preoptic hypothalamus produces fever by disinhibition of presympathetic neurons in the brain stem, but there is yet little understanding of the mechanisms by which factors such as nutritional status and ambient temperature shape the response to the peripheral immune challenge.

Familial Mediterranean Fever without Fever

“…Mutations in the genes encoding pyrin are associated with the distinct interleukin-1β (IL-1β)-mediated autoinflammatory conditions of FMF (16). IL-1β is likely to be the main cause of fever, but attention should be paid to coexisting conditions, such as microsomal prostaglandin E synthase-1 (17). It is reported that the febrile response to lipopolysaccharide-induced IL-1β was lost in chimeric mice that only expressed the microsomal prostaglandin E synthase-1 in hematopoietic cells (18).…”

Interactions between the brain and the immune system in pain and inflammation

“…DNA between two lox sites aligned in the same direction is excised, while DNA between two lox sites facing each other is inverted by Cre (Branda et al 2004).…”

Utilizing network pharmacology to explore the underlying mechanism of Cinnamomi Ramulus in Zika Fever induced by Zika Virus

“…Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis (32).The GO enrichment and KEGG enrichment analysis result showed that CR relieved Zika fever and condition deterioration by regulating the expression of PTGS2 and PTGS1 to further inhibit PG release and regulate metabolism to reduce inflammation response.…”