Fever
How fever works How does fever happen?
Once endogenous pyrogens have been produced by the primary immune response, they must travel to the brain to actually induce fever. After their increased production by activated immune cells, cytokines such as IL-1, IL-6, and TNF are distributed throughout the body through the blood, as they are all soluble proteins. Now, then, these cytokines must have a target to signal and cause a reaction. PGE
As it plays a central role in thermal regulation, it is unsurprising that destruction of the hypothalamus would result in a lack of febrile response; however, experimental evidence shows that direct stimulation of the hypothalamus by IL-1 does not induce fever (6). This potentially contradicting data suggested that although both the hypothalamus and IL-1 appear to be essential to induce fever, as the response will not occur when one of these factors is missing, there must be another link connecting the two, as they do not seem to directly interact. After searching for potential mediators that would convey the signal, the most likely current candidate appears to be prostaglandin E (PGE). This hypothesis is strongly supported by a study in which protein production of a specific PGE receptor was knocked out in mice, resulting in the impairment of febrile response (7). Since the complete signal was eliminated by recombination of the gene for PGE receptor, this appears to confirm that PGE is necessary to transduce the signal responsible for inducing fever to the brain. The use of PGE also appears to be conserved in the febrile response of ectotherms, as it has been shown to play an essential role in signaling fever in toads and salamanders (8).
Set point regulation
To learn more about specifically where in the brain controls for the mechanism of feverish response lie, researchers microinjected rats with PGE (9). They observed distinct responses in the three regions tested (the preoptic anterior hypothalamic area
Once endogenous pyrogens have been produced by the primary immune response, they must travel to the brain to actually induce fever. After their increased production by activated immune cells, cytokines such as IL-1, IL-6, and TNF are distributed throughout the body through the blood, as they are all soluble proteins. Now, then, these cytokines must have a target to signal and cause a reaction. PGE
As it plays a central role in thermal regulation, it is unsurprising that destruction of the hypothalamus would result in a lack of febrile response; however, experimental evidence shows that direct stimulation of the hypothalamus by IL-1 does not induce fever (6). This potentially contradicting data suggested that although both the hypothalamus and IL-1 appear to be essential to induce fever, as the response will not occur when one of these factors is missing, there must be another link connecting the two, as they do not seem to directly interact. After searching for potential mediators that would convey the signal, the most likely current candidate appears to be prostaglandin E (PGE). This hypothesis is strongly supported by a study in which protein production of a specific PGE receptor was knocked out in mice, resulting in the impairment of febrile response (7). Since the complete signal was eliminated by recombination of the gene for PGE receptor, this appears to confirm that PGE is necessary to transduce the signal responsible for inducing fever to the brain. The use of PGE also appears to be conserved in the febrile response of ectotherms, as it has been shown to play an essential role in signaling fever in toads and salamanders (8).
Set point regulation
To learn more about specifically where in the brain controls for the mechanism of feverish response lie, researchers microinjected rats with PGE (9). They observed distinct responses in the three regions tested (the preoptic anterior hypothalamic area