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lauantai 2. kesäkuuta 2018
Fever is the body's natural defence against cancer
Fever is the body's natural defence against cancer
Reducing a fever is one of the first things a doctor tries to do—but a raised body temperature naturally protects us against infection and even tumours, new research has found.
The higher the temperature goes above the 'normal' 37 degrees C (98.6 degrees F), the more the body speeds up its natural defences against tumours, wounds and infections.
Conversely, a low body temperature of around 34 degrees C—which routinely happens when we sleep—can trigger inflammatory processes such as heart disease, which would explain why shift workers or people who suffer from frequent jet lag or insomnia are more prone to inflammatory diseases. Our 24-hour body clock can cope with the natural drop in temperature when we sleep, but the risk of inflammatory disease and cancer rises when it is low for longer periods.
The effects of temperature on health could also explain why cold and flu epidemics are more prevalent in the winter months in the northern hemisphere, say researchers at the Universities of Warwick and Manchester.
A raised body temperature kick-starts the release of a protein, A20, that helps protect the body from inflammatory diseases and cancer. Even small rises in body temperature helps the body's defence systems, the researchers found.
The research echoes a discovery made some years back that found that people who had had a high fever in the previous five years were less likely to develop cancer.
(Source: Proceedings of the National Academy of Sciences, 2018; 201803609; doi: 10.1073/pnas.1803609115)
Temperature regulates NF-κB dynamics and function through timing of A20 transcription
C. V. Harper, D. J. Woodcock, C. Lam, M. Garcia-Albornoz, A. Adamson, L. Ashall, W. Rowe,P. Downton, L. Schmidt, S. West, D. G. Spiller, D. A. Rand, and M. R. H. WhitePNAS May 14, 2018. 201803609; published ahead of print May 14, 2018. https://doi.org/10.1073/pnas.1803609115Edited by Ronald N. Germain, National Institutes of Health, Bethesda, MD, and approved April 27, 2018 (received for review March 7, 2018)
Abstract NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation. _ http://www.pnas.org/content/early/2018/05/09/1803609115 __
from research organizations
Hotter bodies fight infections and tumors better -- researchers show how
The hotter our body temperature, the more our bodies speed up a key defense system that fights against tumors, wounds or infections
Slight rise in temperature and inflammation - such as a fever - speeds up cellular 'clock' in which proteins switch genes on and off to respond to infection.
The hotter our body temperature, the more our bodies speed up a key defence system that fights against tumours, wounds or infections, new research by a multidisciplinary team of mathematicians and biologists from the Universities of Warwick and Manchester has found.
The researchers have demonstrated that small rises in temperature (such as during a fever) speed up the speed of a cellular 'clock' that controls the response to infections -- and this new understanding could lead to more effective and fast-working drugs which target a key protein involved in this process.
Biologists found that inflammatory signals activate 'Nuclear Factor kappa B' (NF-κB) proteins to start a 'clock' ticking, in which NF-κB proteins move backwards and forwards into and out of the cell nucleus, where they switch genes on and off.
This allows cells to respond to a tumour, wound or infection. When NF-κB is uncontrolled, it is associated with inflammatory diseases, such as Crohn's disease, psoriasis and rheumatoid arthritis.
At a body temperature of 34 degrees, the NF-κB clock slows down. At higher temperatures than the normal 37 degree body temperature (such as in fever, 40 degrees), the NF-κB clock speeds up.
Mathematicians at the University of Warwick's Systems Biology Centre calculated how temperature increases make the cycle speed up.
They predicted that a protein called A20 -- which is essential to avoid inflammatory disease -- might be critically involved in this process. The experimentalists then removed A20 from cells and found that the NF-kB clock lost its sensitivity to increases in temperature.
Lead mathematician Professor David Rand, Professor of Mathematics and a member of the University of Warwick's Zeeman Institute for Systems Biology and Infectious Disease Epidemiology (SBIDER), explained that in normal life the 24 hour body clock controls small (1.5 degree) changes in body temperature.
He commented: "the lower body temperature during sleep might provide a fascinating explanation into how shift work, jet lag or sleep disorders cause increased inflammatory disease"
Mathematician Dan Woodcock from the University of Warwick said: "this is a good example of how mathematical modelling of cells can lead to useful new biological understanding."
While the activities of many NF-kB controlled genes were not affected by temperature, a key group of genes showed altered profiles at the different temperatures. These temperature sensitive genes included key inflammatory regulators and controllers of cell communication that can alter cell responses.
This study shows that temperature changes inflammation in cells and tissues in a biologically organised way and suggests that new drugs might more precisely change the inflammatory response by targeting the A20 protein.
Professor Mike White, lead biologist from the University of Manchester, said the study provides a possible explanation of how both environmental and body temperature affects our health:
"We have known for some time that influenza and cold epidemics tend to be worse in the winter when temperatures are cooler. Also, mice living at higher temperatures suffer less from inflammation and cancer. These changes may now be explained by altered immune responses at different temperatures."
C. V. Harper, D. J. Woodcock, C. Lam, M. Garcia-Albornoz, A. Adamson, L. Ashall, W. Rowe, P. Downton, L. Schmidt, S. West, D. G. Spiller, D. A. Rand, M. R. H. White. Temperature regulates NF-κB dynamics and function through timing of A20 transcription. Proceedings of the National Academy of Sciences, 2018; 201803609 DOI:10.1073/pnas.1803609115
University of Warwick. "Hotter bodies fight infections and tumors better -- researchers show how: The hotter our body temperature, the more our bodies speed up a key defense system that fights against tumors, wounds or infections." ScienceDaily. ScienceDaily, 21 May 2018. www.sciencedaily.com/releases/2018/05/180521095606.htm.