11. December 2020
Cortisone – could there be fewer side effects?

Weight gain, thinning skin and diabetes are all side effects of cortisone. Could it be possible for the drug to produce fewer side effects? Researchers in Munich are looking for alternatives.

When someone is ‘taking cortisone’, this usually refers to glucocorticoids – drugs that act like the body’s own hormone cortisol (for example, prednisone or dexamethasone). They are very effective anti-inflammatory drugs. However, people with allergies or asthma often experience side effects from these drugs, which they also feel in their own bodies.

An ideal drug would stop inflammation just as effectively as cortisone – but without severe side effects.


A research team in Munich has now discovered that cortisone drugs in human cells work differently than previously thought. This could lead to new drugs with fewer side effects.


What was the study about?

The study investigated glucocorticoid receptors (GR). These are the places onto which cortisone drugs dock on human cells in order to stop inflammation.


It was previously thought that inflammation stops in three stages: First, the drugs bind to the glucocorticoid receptors. Second, these receptors then dock onto other proteins in the cell. Third, the protein-receptor combination then blocks inflammatory genes in the human genome. It was assumed that the glucocorticoid receptor itself did not come into contact with the genetic material.


What’s new?

The team at the Technical University of Munich discovered that the glucocorticoid receptor must bind to the genetic material (DNA) in order to inhibit inflammation. This means that cortisone drugs work differently from what was believed for years.


Why is this important?

Whether the glucocorticoid receptor binds immediately to the genetic material or first takes a detour via another protein makes an enormous difference for research.


This is because cortisone alternatives have been sought for many years. However, the researchers were looking closely at the connection of protein to protein, which may have led them in the wrong direction. The realisation that the glucocorticoid receptor binds directly to the genetic material opens up new possibilities for developing drugs.


How did the researchers find out?

A special mouse led the scientists to their results: They altered the glucocorticoid receptor of the mouse so that it binds to other protein substances, but no longer directly to the genetic material.

It turned out that glucocorticoids (the cortisone drugs) could no longer inhibit inflammation.


What happens now?

“Now we know that DNA binding plays a major role, yet we have not found a way to separate side effects from the desired effects. That is why we will continue to conduct research”, says Henriette Uhlenhaut, head of the Munich-based research group and professor of ‘Metabolic Programming‘ at the Technical University of Munich.


Original study:

Escoter-Torres L et al.: Anti-inflammatory functions of the glucocorticoid receptor require DNA binding. Nucleic Acids Research 2020, 48 (15): 8393-407



Additional sources

Baumeister Katharina. DNA binding is essential for effectiveness of steroids – Finding cortisone alternatives with fewer side effects. Press release of the Technical University of Munich, 2 September 2020

Tags: treatment