Scientists in Trinity College Dublin (TCD) have discovered new ways of blocking inflammatory cells that can cause complications in a range of diseases, including Covid-19.

The team at the Trinity Biomedical Sciences Institute (TBSI) have discovered two new ways to block inflammatory microphages. These are frontline cells in the immune system, which can become overactive in infected people, causing complications in various diseases.

The scientists have published two papers on this in the Journal of Immunology. The first paper describes how a molecule called 4-OI, which is based on the natural anti-inflammatory molecule itaconate, can block production of an enzyme called COX2.This is critical for prostaglandins, which are lipid compounds that have a key role to play in illness and injury.

“Prostaglandins are very important drivers of acute inflammation and can also cause fever,” explained the lead author of both papers, Ciana Diskin of TBSI’s School of Biochemistry and Immunology.

The first paper supports the use of 4-OI, or molecules based on it, as a wholly new class of anti-inflammatory compounds, which could prove useful in several diseases, including COVID-19. 

The second paper looks at how another molecule, called I-3-P, which is derived from parasites called Trypanosomes, can also be an inhibitor of prostaglandins. The scientists suggest that this might help Trypanosomes survive in their infected hosts, since it will limit the inflammatory response against the parasite. This provides a good example of how a pathogen can manipulate the host it is infecting for its own survival.

According to the papers’ senior author, Prof Luke O’Neill, a professor of biochemistry at TCD, these two papers “reveal new mechanisms to limit inflammatory macrophages, which could have use in multiple diseases”.

“We have found that 4-OI, which is based on an anti-inflammatory factor made in our own bodies, and I-3-P, a molecule made by an infectious pathogen, can both block COX2 and prostaglandins, possibly providing us with new anti-inflammatory strategies,” he said.