Researchers from the Trinity Biomedical Sciences Institute (TBSI) have published two papers detailing potential new mechanisms to block overactive inflammatory macrophages, a type of front-line immune cell implicated in a number of diseases.
The papers, published in the Journal of Immunology, detail two different anti-inflammatory molecules, 4-octyl-itaconate (4-OI) and indole-3-pyruvate (I-3-P), which inhibit prostaglandin production from macrophages.
“Prostaglandins are very important drivers of acute inflammation and can also cause fever”, Ciana Diskin, the papers’ first author, said in a press statement.
“These two publications reveal new mechanisms to limit inflammatory macrophages, which could have use in multiple diseases”, added Prof Luke O’Neill, the senior author on both papers.
“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”, O’Neill said.
COX2 is an important enzyme for prostaglandin production and is blocked by 4-OI, a derivative of the naturally occurring anti-inflammatory molecule itaconate. This points to 4-OI and its derivatives as a potential new class of anti-inflammatory compounds that can be used for therapeutics.
I-P-3 also blocks COX2 but is derived from trypanosomes, the parasites that cause African sleeping sickness. The paper authors postulate that this immune modulation may allow the trypanosomes to evade the immune system and prolong both parasite and host survival.
Both of these new compounds will undergo further research and testing and may lead to a new approach to anti-inflammatory drugs.
