In infections and inflammatory diseases, the immune system creates a group of small signalling molecules, or cytokines. One of these – interleukin 6 – is necessary for the body to combat fever. Researchers at Linköping University are now able to show for the first time how this process works.
The mechanism behind this interaction has so far been uncertain. But in this study, now being published in The Journal of Neuroscience, the research team under the leadership of Professor Anders Blomqvist has been able to solve the problem. They have shown how the chain of events that leads to fever begins with interleukin 6 binding to the receptor substance on the surface of the small blood vessels of the brain.
Activates a signalling systemThis binding activates a signalling system in the walls of the blood vessels, which in turn sets off the production of prostaglandin E2. This is a substance that causes fever through direct action on nerve cells in the part of the frontal lobe that regulates temperature - the body’s “thermostat”.
When the researchers, using genetic methodology, removed the receptor substance for interleukin 6 from the blood vessels of the brain, the production of prostaglandin was reduced as was the animal's ability to develop a fever. The same thing happened when they removed a signalling molecule inside the cells of the blood vessels which is attached to the receptor substance. The study is a continuation of the earlier work by the same group on the mechanisms behind fever.
Significance for the treatment of neurological diseases“This is fundamental research, the aim of which is to understand how the brain is affected by immune signals from the body. There are still important questions to be answered, such as how various cytokines interact to shape the brain's response to peripheral inflammation. In the long term our research will have significance for the treatment of different neurological diseases that are known to have inflammatory elements, for example neurodegenerative diseases such as Alzheimer’s, but also psychological diseases such as depression,” says Professor Blomqvist.
Article: Immune-induced fever is mediated by IL-6 receptors on brain endothelial cells coupled to STAT3-dependent induction of brain endothelial prostaglandin synthesis by Anna Eskilsson, Elahe Mirrasekhian, Sylvie Dufour, Markus Schwaninger, David Engblom and Anders Blomqvist. The Journal of Neuroscience, 26 November 2014.