Anticancer can drugs can limit inflammation, meaning they could be used as a sepsis treatment, according to researchers in Portugal.
According to researchers from Instituto Gulbenkian de Ciência (IGC), the anticancer drug, anthracycline can limit the unrestrained production of inflammatory mediators in the immune system. The discovery could position the drug as a potential sepsis treatment, which kills more than oncologic disease. The data also revealed previously unknown mechanisms that likely contribute to the drugs’ effectiveness in chemotherapy.
The study has been published in eLife.
Sepsis treatment is difficult
Sepsis kills around 11 million people globally each year. In order to survive sepsis, the patient needs get rid of affection and limit the damage to the organs caused by the immune response.
A group of researchers from IGC focused on immune response damage, which is still not a regular part of the therapeutic interventions for sepsis. The researchers then explored the possibility of anthracycline as a sepsis treatment.
Previously, the team have shown that these drugs can prevent organ failure in mice with sepsis without affecting the infectious agent’s burden. After this discovery, a clinical trial in Germany was conducted to evaluate whether the use of anthracyclines could improve the course of sepsis treatment and reduce the risk of death in patients.
In order to realise the full potential of the drugs, the realise needed to understand how to create a tolerance to the infection.
How do anthracyclines work?
To understand this, researchers tested different anthracyclines in the immune system cells of mice. The researchers were surprised by the results. The anthracyclines limited the levels of pro-inflammatory mediators produced by the cells when administered in low doses. This effect continued when researchers treated sepsis in with these drugs. The researchers then wanted to understand how these drugs control inflammation.
“We discovered that anthracyclines control relevant inflammatory genes in the immune system cells”, explained Ana Neves-Costa, a researcher at the IGC and co-author of the study.
Anthracyclines avoid the binding of factors that drive the expression of these genes by forming a complex with the cell’s DNA. This causes the two cells produce fewer inflammatory molecules.
“This new mechanism is particularly important because it lacks the side effects caused by administering high doses of these compounds in chemotherapy,” added Neves-Costa
“With this work we found a possible new solution to treat diseases caused by exaggerated inflammation, such as sepsis and rheumatoid arthritis, more effectively,” explained Luís Moita, principal investigator of the study.
“Given that these drugs are already approved for use in the clinics, repurposing these for new treatments will be much easier than starting from scratch,” added Moita.
The researchers also believe the regulation of gene expression and the limitation of inflammation described in this study could contribute to the effectiveness of anthracyclines in cancer treatment.