Researchers from Washington University in St. Louis found that itaconate, a compound produced by inflammatory cells, relieved psoriasis-like symptoms in mice. It targets the IL-17 pathway, which plays a key role in autoimmune disease, so while the research centered on psoriasis, it could have broader applications.
Inflammation is an immune response against infection, but it sometimes goes awry and targets the body's healthy tissues. Macrophages—inflammatory cells that detect and destroy bacteria—are part of this response. They produce itaconate, which dampens inflammation, the scientists found.
"Since we first linked itaconate to inflammatory cell activation in 2016, it has been surprising us," said Maxim Artyomov, Ph.D., an assistant professor of pathology and immunology at Washington University, in a press release. "Everyone thought that if it is produced by inflammatory cells it should fight infection, but no—it's anti-inflammatory. 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."
To figure out how it works, the team treated inflammatory cells from humans and mice with dimethyl itaconate, a modified version of the compound. It lowered levels of IkappaBzeta, a protein in the IL-17 inflammatory pathway that has been linked to differing risk of developing psoriasis. The researchers then administered the compound to mice with psoriasis-like symptoms in their ears.
The mice received daily doses of dimethyl itaconate or placebo for seven days. At the end of treatment, the team saw that mice in the placebo group had red and swollen ears, while the ears of the treated mice looked normal. Their study appeared in the journal Nature.
Psoriasis treatments, such as topical creams and light therapy, aim to reduce inflammation and clear the skin. Patients who do not respond to either may receive systemic treatment.
Some up-and-coming treatments are taking a different approach to the autoimmune disease. Exicure is developing a topical antisense treatment for psoriasis that targets TNF mRNA in the hope of reducing symptoms. And scientists from Emory and Case Western Universities are working on two compounds inspired by a component of fire ant venom that showed promise in mice with psoriasis.
Because IL-17 is implicated in many autoimmune diseases, it could be useful in the treatment of other illnesses, including multiple sclerosis. Encouraged by structural similarities between dimethyl itaconate and dimethyl fumrate, the active ingredient in an FDA-approved MS drug, Artyomov and his team are already looking into the effects of itaconate compounds in mouse models of MS.