The same compound that helps immune cells detect bacteria during an invasion could help scientists design a new drug to treat psoriasis, an autoimmune disease. From the Washington University School of Medicine, researchers use a modified form of a compound called itaconate in mice models of psoriasis.
"We are taking advantage of the body's own anti-inflammatory power and showing that it can help in real situations when your own immune system is hurting you," explained senior author Maxim Artyomov, PhD.
Psoriasis is an autoimmune disease characterized by accelerated growth of skin cells that the body can’t shed. Instead, the cells build up on the skin, causing the characteristic patches, often on the knees, elbows, lower back, or scalp.
Inflammation is a double-edged sword. Inflammation (redness, swelling) is necessary for recruiting immune cells to the scene of an infection or injury to ward off pathogens and heal wounds, but the hero turns villanous when the inflammation is excessive or unwarranted.
Itaconate suppresses inflammation, which is the foundational issue behind autoimmune diseases like psoriasis, rheumatoid arthritis, lupus, and others. While the present study looked at the potential of itaconate to treat psoriasis, the compound may also be capable of treating other diseases too.
The main focus of the present study was identifying how and why itaconate suppresses inflammation. Researchers started by treating isolated inflammatory cells from mice and humans with a modified form of itaconate, dimethyl itaconate. They saw that the compound reduces levels of a key protein in the IL-17 inflammatory pathway, lkappaBzeta.
This inflammatory pathway is significant in the fight against bacteria and other pathogens, but it’s also partially responsible for causing autoimmune diseases. Genetic studies linked variations in the gene that codes for lkappaBzeta to an increased risk for developing psoriasis. Would reducing levels of lkappaBzeta treat psoriasis?
In the mice, researchers induced psoriasis-like symptoms while giving them doses of either placebo or dimethyl itaconate once a day for one week. Dimethyl itaconate successfully thwarted psoriasis as opposed to the placebo. Follow-up studies already in progress include testing itaconate compounds and multiple sclerosis in mice.
“Everyone thought that if it is produced by inflammatory cells it should fight infection, but no - it's anti-inflammatory,” Artyomov said. “Now we know that itaconate compounds can help with autoimmune diseases, specifically in psoriasis and potentially in multiple sclerosis. This small molecule is turning out to be really powerful."
The present study was published in the journal Nature.