Itaconate, a new frontier in autoimmune disease therapies
Itaconate, a new frontier in autoimmune disease therapies
Zahra farokhi,1,*Farzaneh karampour,2Melina Foroudastan,3Mohammad Hossein Matoori,4Nasrin Zare,5
1. School of Medicine, Najafabad Branch, Islamic Azad University, Najafabad, Iran 2. School of Medicine, Najafabad Branch, Islamic Azad University, Najafabad, Iran 3. School of Medicine, Najafabad Branch, Islamic Azad University, Najafabad, Iran 4. School of Advanced Medical Technologies, Isfahan university of medical science, Isfahan, Iran 5. Assistant professor, Najafabad Branch, Islamic Azad University, Najafabad, Iran
Introduction: Itaconic acid, a naturally occurring compound produced in the Krebs cycle, has
garnered attention in recent years due to its potential effects on autoimmune diseases. The
Krebs cycle is a series of biochemical reactions that occur in the mitochondria of cells, playing
a vital role in generating energy for cellular functions. Itaconate role in this metabolic pathway
highlights its significance in cellular metabolism and potential implications for autoimmune
diseases. Autoimmune diseases occur when the immune system mistakenly attacks healthy
cells in the body. In this article, we will explore the impact of itaconate on autoimmune
diseases.
Methods: Our study was conducted on the PubMed database using the keywords (Disease
AND Autoimmune) OR (Diseases AND Autoimmune) OR "Autoimmune Disease" OR
"Autoimmune Diseases") AND ("itaconate" OR "methylenebutanedioic acid" OR "methylene
succinic acid" OR ("itaconic acid" AND "sodium salt") OR ("itaconic acid" AND "disodium
salt") OR "methylidenebutanedioate" OR ("itaconic acid" AND "calcium salt") OR ("itaconic
acid" AND "copper salt") OR "itaconic acid") from 2018 to 2024. Out of 23 papers related to
this topic, seven studied were reviewed
Results: Some previous studies are pointing to itaconate as a possible solution for
inflammation, especially in autoimmune and inflammatory issues. It kicks off a process in cells
called Nrf2, which then helps cut down on collagen production in skin cells, lowers the creation
of harmful free radicals, and stops the stimulation of collagen proteins. In mouse models of
lupus, Itaconate treatment improved kidney structure, lowered autoantibody levels, and
positively impacted platelet counts and lymphoid organ function. Additionally, in autoimmune
hepatitis, Itaconate effectively reduced necrotic areas, liver enzyme levels, inflammatory cell
infiltration, and cytokines. For type 1 diabetes, Itaconate showed preventative effects against
glycemic deterioration, increased islet cell numbers, lowered blood sugar levels, and restored
insulin-producing beta cells. Furthermore, Dimethyl itaconate, a derivative of Itaconate
displayed protective effects in encephalomyelitis by improving outcomes and reducing disease
severity. DMI treatment strengthened the blood-brain barrier, suppressed the activation of
microglia, increased the expression of Nrf2 and HO-1, inhibited the movement of T cells into
the central nervous system, and directly blocked the development of harmful T cells.
Conclusion: Based on our review, Itaconate and its derivatives, show significant anti-
inflammatory properties by activating Nrf2, reducing cytokine expression and oxidative stress
in autoimmune diseases like lupus nephritis, type 1 diabetes, and systemic sclerosis. Therefore,
these findings suggest the therapeutic promise of Itaconate derivatives in autoimmune
disorders, Necessitating further clinical investigation.