eLife: Cancer drugs are the new hope for sepsis treatment

The body's extreme response to infection, a disease called sepsis, kills 11 million people each year
.
This is because to survive a serious infection, it is not enough to get rid of the source of infection, which is currently relatively effective; It is also necessary to limit the damage these and immune responses cause to
organs.
The IGC's Innate Immunity and Inflammation Research Group focuses on this second aspect, which is still not part of
sepsis treatment interventions.

The solution could be a class of drugs commonly used to treat cancer: anthracyclines
.
In the past, the team demonstrated that these drugs could prevent organ failure
in sepsis-affected mice without affecting the burden of infectious agents.
The findings inspired a clinical trial in Germany that is evaluating whether the use of anthracyclines improves the course of sepsis and reduces the risk
of death in patients.
But to get the most out of these drugs, we need to understand how they become resistant to infections
.

To explore this, the researchers tested different anthracyclines
in mouse immune system cells.
The results were surprising: these anti-cancer drugs limited the levels of
pro-inflammatory mediators produced by cells when used at low doses.
This effect was maintained
when the researchers treated mice with sepsis with these drugs.

The next challenge is understanding how these drugs control inflammation
.
Ana Neves-Costa, IGC researcher and co-author of the study, explains: "We found that anthracyclines control relevant inflammatory genes
in immune system cells.
" By forming complexes with the cell's DNA, these drugs avoid binding
to the factors that drive the expression of these genes.
As a result, cells produce fewer inflammatory molecules
.
"This new mechanism is particularly important because it does not have the side effects
caused by the use of high doses of these compounds in chemotherapy," the researchers added.

"With this work, we identified a possible new solution that could more effectively treat diseases caused by excessive inflammation, such as sepsis and rheumatoid arthritis," explains Luís Moita, a trained doctor at the IGC and principal investigator
who led the study.
"Given that these drugs are already approved for clinical use, it will be much
easier to repurpose them for new treatments than to start from scratch," he added.
The regulation of gene expression and the limitation of inflammation described in this study may also contribute to the effectiveness of anthracyclines in cancer treatment, which has not been previously recognized
.