For patients with leukemia, receiving a bone marrow or blood stem cell transplantation is essential, however, the transplantation results in complications in almost every second patient: The transplanted immune cells, especially T cells, not only attack the cancer cells but also healthy tissue. This leads to severe inflammatory reactions, especially in the skin and intestine. Even with drug prophylaxis and treatment, acute Graft-versus-Host Disease (GvHD) often is fatal.

GvHD may develop as a consequence after the treatment of leukemia when immune cells from a transplant are overactive and harm the healthy tissue of the recipient patient. It was discovered by researchers from the University Medical Center Freiburg and the University of Freiburg's Cluster of Excellence CIBSS that an endogenous chemical can reduce this inappropriate immune response.

A group of scientists at the University Medical Center Freiburg and the Centre for Integrative Biological Signaling Studies (CIBSS), a Cluster of Excellence of the University of Freiburg, looked into whether human beta-defensin 2 (hBD-2) affects inflammation in GvHD. They discovered that giving hBD-2 to mice with acute GvHD dramatically reduced disease severity and mortality. The encouraging findings were released in the journal Science Translational Medicine.

The initial comparison made by the researchers involved hBD-2 levels in the intestinal tissue of patients with acute GvHD, ulcerative colitis patients, and healthy volunteers. "Although both diseases are characterized by inflammatory processes in the intestine, hBD-2 was only increased in patients with ulcerative colitis, not in patients with acute GvHD," says Köhler, describing the observations from gene expression analyses and microscopic examinations.

The next step was to determine whether giving mice hBD-2 had any impact on how quickly their acute GvHD developed. Indeed, mice who got hBD-2 had less allogeneic T cell response in their gut. The molecule's impact on signaling pathways that cause the activation of dormant T cells was the cause of this effect, according to the researchers. They also found that the treatment of hBD-2 altered the bacterial ecology in the mice's intestines and reduced the amount of neutrophil immune cells that migrated into the intestinal tissue, thereby lowering their contribution to the inflammatory response there. 

These findings make hBD-2 an attractive prospect for further investigation and clinical trials, and they suggest that it may one day be used as a preventive in allogeneic stem cell transplantation.