New mechanism of cortisone action deciphered

Cortisone has been used for decades to treat chronic inflammation, for example is patients with rheumatic diseases; however, the underlying molecular mechanism of action was largely unclear. A research team led by Prof Dr Gerhard Krönke (Charité and DRFZ) and involving Prof Dr Eicke Latz (DRFZ and Charité) has now discovered that cortisone reprograms the metabolism of immune cells, which activates the body’s own inflammatory brake. These findings enable the development of anti-inflammatory drugs with fewer side effects and have recently been published in the journal Nature.

The study focussed on macrophages, immune cells that play a crucial role in chronic inflammation such as rheumatic disease. The researchers found that cortisone not only influences genes, but also reverses changes in cell metabolism triggered by inflammatory stimuli. This mechanism particularly affects the production of the anti-inflammatory molecule itaconate. Itaconate is secreted by mitochondria, the energy power engines of the cells. During inflammation, however, mitochondria switch their metabolism to “defence” and itaconate production is inhibited. Permanent failure of the immune brake leads to chronic inflammation. Cortisone can reprogramme the metabolism of the macrophages and thus stimulate the production of itaconate in these cells, thereby inhibiting inflammation.

Several teams were involved in the study from the Medical Clinic for Rheumatology Charité-Universitätsmedizin Berlin, DRFZ, University Hospital Erlangen and the University of Ulm.