Hotter bodies fight infections and tumours better—researchers show how

[Indigophoton]

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.

The article, https://m.medicalxpress.com/news/2018-05-hotter-bodies-infections-tumours-betterresearchers.html

Temperature regulates NF-κB dynamics and function through timing of A20 transcription

Significance
Inflammation is often accompanied by temperature change, but little is known about the role of temperature in the inflammatory response. We show that physiologically relevant temperature changes significantly perturb NF-κB dynamics following TNFα stimulation in single cells. Using experimentation informed by mathematical modeling, we found that these changes were mediated, at least in part, through the key feedback gene TNFAIP3/A20. Curtailing A20 expression removed temperature sensitivity across the fever range (37 °C to 40 °C). Gene expression was generally unaffected between these temperatures, although a select set of NF-κB−regulated genes was up-regulated at early time points. These genes were predominantly involved in inflammation, signaling, and cell fate. The cellular response to inflammation may therefore be mechanistically and functionally regulated by temperature.

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.

The paper, http://www.pnas.org/content/early/2018/05/09/1803609115