Into thin air: How the immune system reacts to oxygen deficiency
As the "element of life", the organism needs oxygen not only to breathe. Every cell in the human body is dependent on oxygen. But how does our immune system react to a lack of oxygen? Does this factor influence inflammatory reactions or tumor development? Scientists at the University of Duisburg-Essen want to answer these important questions with a new interdisciplinary research approach.
Oxygen consumption in cells and tissues is regulated by the hypoxia-inducible factor (HIF), for whose discovery the Nobel Prize in Physiology or Medicine was awarded in 2019. Professor Joachim Fandrey with the team of the Institute of Physiology of the Medical Faculty of the University of Duisburg-Essen has been intensively researching the regulatory mechanisms of HIF, which is, for example, pivotal for tumor development as well as inflammatory processes. However, these findings have so far been obtained almost exclusively in animal models and in vitro approaches. Whether and to what extent these findings are found in real life situations in humans is largely unclear, because suitable and ethically justifiable investigation models have been lacking up to now.
In order to close this knowledge gap, the research groups of the Institutes of Physiology and Medical Psychology and Behavioral Immunology as well as the Clinics of Infectious Diseases and Nephrology have joined forces in an innovative research project, which is led by Dr. Bastian Tebbe within the framework of the UMEA Clinician Scientist Program.
Healthy male volunteers are administered either a placebo or lipopolysaccharide (LPS) intravenously. LPS activates the immune system and elicits a systemic inflammatory response lasting several hours. This is followed by a stay of several hours in the altitude training center bewegungsfelder in Essen-Rüttenscheid. In the altitude training chamber, the oxygen content in the air is only 11% instead of the usual 21%, which corresponds to an altitude of about 4300 meters.
Through this interdisciplinary approach with working groups from four participating institutes and clinics, the reaction of the immune system to the lack of oxygen can be analyzed from a wide variety of perspectives and with a wide variety of methods, ranging from molecular biological approaches, immunological and endocrine analyses to questionnaires on sensitivities as well as attention and reaction tests.
Through this innovative experimental approach, new insights into the function of immunocompetent cells are expected, which will allow conclusions to be drawn about the occurring dysregulation of the immune system in severe and life-threatening infections (sepsis).
"This project is an excellent example of combining clinical work and research. It was therefore obvious to plan the project within the framework of the Clinician Scientist Program (UMEA) of the Medical Faculty," explain physiologist Joachim Fandrey and behavioral scientist Manfred Schedlowski.