New solution to treat diseases caused by exaggerated inflammation

A recent study guided by the Instituto Gulbenkian de Ciência (IGC) shows how anticancer drugs reduce inflammation, establishing them as prospective sepsis treatments.

New solution to treat diseases caused by exaggerated inflammation

Image Credit: Instituto Gulbenkian de Ciência.

The research, published in eLife, demonstrates that this class of cancer treatment drugs reduces the immune system's unregulated production of inflammatory mediators. The discovery places these medications as viable treatments for inflammatory disorders like sepsis, which kills as many people as cancer does. The findings also show previously undiscovered processes that may contribute to the efficacy of these drugs in chemotherapy.

Every year, 11 million individuals die from sepsis, the body’s severe response to infection. This is because, to survive a significant infection, it is vital to minimize the damage that the infectious agent and the immune response impose on the organs, which is now done with relative efficacy.

The Instituto Gulbenkian de Ciência (IGC) Innate Immunity and Inflammation research group concentrates on this second aspect, which is still not part of the treatment strategy for sepsis.

Anthracyclines, a type of drug often used to treat cancer, could be the answer. Previously, the researchers proved that these drugs reduce organ failure in sepsis mice without modifying the infectious agent’s burden. This discovery sparked clinical research in Germany to see if using anthracyclines enhances the course of sepsis and lowers the chance of death in patients. However, in order to fully benefit from these drugs, researchers must first comprehend how they confer infection tolerance.

To investigate this, researchers examined various anthracyclines in mice’s immune system cells. When delivered in low dosages, these anticancer drugs reduced the levels of pro-inflammatory mediators produced by the cells. This effect was sustained when these drugs were administered to sepsis-infected mice.

The next step was to figure out how these drugs reduce inflammation.

We discovered that anthracyclines control relevant inflammatory genes in the immune system cells.”

Ana Neves-Costa, Study Co-Author and Researcher, Instituto Gulbenkian de Ciência

These drugs prevent the binding of factors that induce the expression of these genes by building a complex with the cell’s DNA. Cells create less inflammatory molecules as a result.

This new mechanism is particularly important because it lacks the side effects caused by administering high doses of these compounds in chemotherapy.”

Ana Neves-Costa, Study Co-Author and Researcher, Instituto Gulbenkian de Ciência

Luís Moita, a doctor by training and principal investigator at the IGC leading the study, details, “With this work we found a possible new solution to treat diseases caused by exaggerated inflammation, such as sepsis and rheumatoid arthritis, more effectively. 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.”

It is also possible that the previously unknown regulation of gene expression and limiting of inflammation documented in this work contribute to the efficacy of anthracyclines in cancer treatment.

Source:
Journal reference:

Chora, A. F., et al. DNA damage independent inhibition of NF-κB transcription by anthracyclines. eLife. doi.org/10.7554/eLife.77443.

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