Researchers Reveal Novel Inflammation Pathway

Novel Inflammation Pathway

Inflammation is an essential process that occurs in the organism. It is responsible for the protection of the body, through the destruction of harmful stimuli, such as bacteria and viruses, while also removing damaged or dead cells. However, if the process is either chronic or incorrectly controlled, it is responsible for various diseases, such as Chron’s disease, rheumatoid arthritis, asthma, tuberculosis, etc. Chronic inflammation can also lead to sepsis, which is a potentially fatal immune reaction that occurs when the inflammation is triggered throughout the whole organism. The study is led by professor Luke O’Neill, from the TCD (Trinity College Dublin) and it was recently published in the journal Nature.

A research team from the UCD (University College Dublin), in Ireland, reveals a novel signal that is a trigger for the inflammatory response against bacterial infections. In their studies they also managed to block this newly discovered signal in laboratory animal models. According to the researchers involved, the presence of bacteria in the organism triggers the macrophages, which change their energy burning pattern. Macrophages are immune cells that ingest diseased, dead cells or foreign microorganisms. The change in their burning pattern leads to the accumulation of succinate in the cells, which subsequently triggers a series of biochemical events that stimulates the onset of inflammation.

Chronic Inflammation

One part of the biochemical events involves a small molecule known as HIF-1a (hypoxia-induced factor 1a). This molecule is responsible for the organism’s adaptation to low oxygen situations. Professor Cormac Taylor, one of the researchers of the study, explains that, “when you go to high altitude, this factor gets expressed in cells and that helps to increase the number of red blood cells in your blood, so you can adapt to the lower oxygen”. However, that is not the sole function of HIF-1a. According to professor Taylor, the molecule’s pathway also activates during stress. Previous studies show that the activation of HIF-1a is present in inflammatory bowel disease. Together with Dr Eoin Cummins, professor Taylor discovered that when macrophages sense a threat posed by bacteria, they build-up succinate, which causes the HIF-1a molecule to switch ‘on’ the IL-1 (interleukin-1) gene. IL-1 is a very potent  pro-inflammatory gene which contributes to the onset of the inflammatory process.

The current study reveals the important connection between the macrophages’ energy burning processes that occur during the immune process and the onset of inflammation. Moreover, the research team also shows that the activity of the succinate/HIF-1a was partially blocked by a drug that’s currently being used to treat epilepsy. The effect was achieved in a laboratory animal model with sepsis. “It’s a big emerging area, the links between metabolism, or energy burning, and inflammation in disease”, concluded professor Taylor.