Immune modulatory medications have dual effect

Drugs used to treat inflammatory rheumatic diseases and skin cancer affect bone health

Anti-inflammatory medications which are used to treat rheumatoid arthritis protect the skeleton, while preparations which increase immune response and are prescribed to treat melanoma (a type of skin cancer) damage it. Activating or inhibiting a particular enzyme which is produced naturally in the body affects not only the inflammatory response but also the number of cells known as osteoclasts which break down bone. Researchers at FAU and at Universitätsklinikum Erlangen have observed this effect. They recently published their findings in the journal Science Translational Medicine.*

Most processes in the human body are controlled by enzymes. By carrying out experimental investigations and evaluating data from patients who were suffering from rheumatoid arthritis or melanoma, the researchers discovered that activating or inhibiting the body’s natural enzyme IDO (indolamine 2,3-dioxygenase) not only stops or increases inflammatory reactions respectively, it also has an influence on the number of osteoclasts. ‘IDO is crucial for the immune system and the bones,’ emphasises Prof. Dr. Aline Bozec, Department of Medicine 3 – Rheumatology and Immunology at Universitätsklinikum Erlangen and head of the international working group.

In the human body, IDO is the most important enzyme for breaking down the amino acid tryptophan into the hormones serotonin and melatonin. The body is unable to produce this amino acid itself, meaning it has to be obtained from food, such as chocolate. ‘We have shown that medications which stimulate the IDO enzyme inhibit osteoclasts in the body and therefore protect the bones,’ explains Prof. Dr. Bozec. These kinds of drugs are currently used to treat exaggerated immune response in diseases such as arthritis or to prevent transplant rejection.

These preparations mimic the body’s natural protein CTLA-4 and stimulate the IDO enzyme, reducing the number of osteoclasts which in turn protects the bones. The fact that activating IDO reduces the breakdown of bone was previously unknown. In healthy people, cells known as osteoblasts which form bone balance out the effect of the osteoclasts which break it down. ‘Discovering this way in which medications can regulate the immune system expands our knowledge of the effects of immunosuppressants which counteract inflammatory bone and joint diseases and osteoporosis,’ explains Prof. Dr. Georg Schett, head of the Department of Medicine 3 – Rheumatology and Immunology at Universitätsklinikum Erlangen.

This has also led the researchers to investigate a cancer drug which is used to treat melanoma. ‘In some cases of metastatic melanoma, we are able to achieve astounding treatment success using CTLA-4 inhibitors,’ explains Prof. Dr. Lucie Heinzerling from the Department of Dermatology (head of department: Prof. Dr. Gerold Schuler) who was also involved in the study. The aim of these medications is to increase immune response. ‘We suspected that IDO plays a role in fighting tumours in treatment using CTLA-4 inhibitors. The inhibitors reduce the activity of the enzyme. At the same time, the number of cells which break down bone is increased. This is a very important discovery and will be of lasting significance for our patients’ treatment,’ emphasises Prof. Dr. Heinzerling.

With this work, Prof. Dr. Aline Bozec, who began her career at leading cancer research centres in Vienna and Madrid, has discovered a significant path of communication between the immune system, tumour and bones in the human body. At the same time, the findings are a success for the strong translational research focus of the Faculty of Medicine at FAU.

Further information:

Prof. Dr. Aline Bozec
Phone: +49 9131 8539109
aline.bozec@uk-erlangen.de