Endogenous citraconic acid inhibits viruses and strengthens the immune system
A German research team has for the first time described the hitherto unknown effect of an endogenous molecule called citraconic acid. The substance protects cells with its antioxidant and anti-inflammatory properties. Additionally, citraconic acid inhibits the release of influenza viruses from human cells.
A joint working group of TWINCORE, the Helmholtz Center for Infection Research and the Helmholtz Institute for Pharmaceutical Research Saarland analyzed the endogenous substance citraconic acid, which has the potential to improve the human immune system. The results were recently presented in the renowned journal "Nature Metabolism".
What is citraconic acid?
The three substances itaconic acid, mesaconic acid and citraconic acid are naturally present in the human body. “Itaconic acid has two isomers, i.e. natural relatives that differ only slightly in their chemical structure, mesaconic acid and citraconic acid,” says research director Dr. Frank Pesler.
All three substances are found in higher organisms such as humans. Researchers around Dr. Peßler were able to detect the three substances in the lymph nodes and the spleen for the first time in 2021. These two organs play a central role in the immune system.
"We then further characterized these isomers," says Peßler. Citraconic acid in particular has been shown to have enormous potential for the development of new drugs that improve cell protection, inhibit viruses and strengthen the immune system.
What is the role of citraconic acid in the body?
According to the research team, citraconic acid has several positive effects on the immune system. “We found that citraconic acid activates an important signaling pathway in the immune system,” Peßler points out.
According to him, this is the so-called NRF2 pathway. This controls antioxidant and anti-inflammatory processes that can protect cells from harmful influences. Citraconic acid develops a stronger effect at this stage than the two related endogenous substances, itaconic and mesaconic acid.
Citraconic acid inhibits influenza viruses
In another experiment, researchers infected human cells with influenza viruses and simultaneously treated the cells with citraconic acid. The team was able to observe a strong inhibition of the messenger substances that trigger inflammation.
"It inhibits type 1 interferon signaling cascades and thereby reduces pro-inflammatory cytokines and chemokines," Pessler describes. Cytokines and chemokines are signaling molecules that initiate and enhance immune system processes.
Also in this series of tests, citraconic acid had the strongest antiviral properties. The molecule was able to almost completely prevent the release of viral particles from infected cells.
Citraconic acid could also help with COVID-19
Peßler and his team hope that new drugs based on citraconic acid can be developed to fight serious viral infections such as influenza and COVID-19.
Hope for a cure for blood poisoning
Citraconic acid could also be used for sepsis, which often occurs as a complication of infections or after operations.
As the researchers discovered, citraconic acid prevents the production of itaconic acid. “Too much itaconic acid can weaken the immune system,” added Dr. Fangfang Chen from the study team.
"The administration of citraconic acid could therefore lead to an increase in the performance of the immune system", specifies the scientist. According to Chen, this could be used in a targeted way, for example to boost the immune system in cases of advanced blood poisoning.
Citraconic acid may also help against cancer
"Other research groups have shown that itaconic acid can promote the growth of certain tumors," Pessler points out. Since citraconic acid inhibits itaconic acid, a new class of anti-cancer drugs based on citraconic acid could emerge.
The working group has already filed a patent application for the medical use of citraconic acid. "However, we still have a lot of work to do before knowing if and how citraconic acid-based drugs can best be used", summarizes Dr. Pesler. (vb)
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This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Graduate editor (FH) Volker Blasek
Sources:Chen F, Elgaher WAM, Winterhoff M et al. Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cellular metabolism; in: Nature's Metabolism (2022). nature.comTWINCORE - Center for Experimental and Clinical Infection Research: Cell protection, immunomodulation and virus inhibition by an endogenous substance (published July 7, 2022), twincore.de
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.